Ultragenyx Enters Strategic Collaboration with Solid Biosciences for DMD Gene Therapies

Rare Daily Staff

Ultragenyx Pharmaceutical will pay Solid Biosciences $40 million upfront as part of a strategic collaboration and license agreement to focus on the development and commercialization of new gene therapies for Duchenne muscular dystrophy, a rare, genetic muscle disease.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle deterioration and weakness. It is the most common type of muscular dystrophy. DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. The first symptoms are usually seen between three and five years of age and worsen over time. Most patients require full-time use of a wheelchair in their early teens, and then progressively lose the ability to independently perform activities of daily living such as using the restroom, bathing and feeding. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and patients usually succumb to the disease in their twenties.

The parties will collaborate to develop products that combine Solid’s differentiated microdystrophin construct, Ultragenyx’s HeLa producer cell line manufacturing platform, and AAV8 variants. The collaboration also brings together Solid’s expertise in muscle biology and Ultragenyx’s expertise in bringing novel therapies to patients with rare diseases.

Under the terms of the collaboration, Solid granted Ultragenyx an exclusive license for any pharmaceutical product that expresses Solid’s proprietary microdystrophin construct from AAV8 and variants for use in the treatment of Duchenne and other diseases resulting from lack of functional dystrophin, including Becker muscular dystrophy.

In addition to the upfront payment, Ultragenyx has agreed to pay up to $255 million in cumulative milestone payments per product upon achievement of specified milestone events, and tiered royalties on worldwide net sales at low double digit to mid-teens percentages. Upon achievement of proof-of-concept, Solid has the right to opt-in to co-fund collaboration programs in return for participation in a profit share or increased royalty payments.

“We believe that Solid’s microdystrophin is best-in-class with its unique neuronal nitric oxide synthase binding domain,” said Emil Kakkis, CEO and president of Ultragenyx. “By using an AAV8 variant validated in prior human and other studies combined with our scalable, efficient HeLa producer cell line platform, we believe we can leverage our mutual strengths to develop a high-quality AAV-based treatment alternative for Duchenne.”

Solid’s proprietary microdystrophin construct has exhibited functional benefit in preclinical models. In preclinical studies, animals expressing a microdystrophin capable of restoring neuronal nitric oxide synthase (nNOS) resisted fatigue better than those expressing a microdystrophin that does not.

Photo: Emil Kakkis, CEO and President of Ultragenyx