Rare Daily Staff

The U.S. Food and Drug Administration granted Denali Therapeutics Rare Pediatric Disease Designation for the company’s DNL310, its enzyme replacement therapy for patients with mucopolysaccharidosis II (MPS II), a rare lysosomal storage disorder.

MPS II, also known as Hunter Syndrome, is caused by a deficiency of the iduronate 2-sulfatase (IDS) enzyme. Approximately two-thirds of patients with Hunter Syndrome suffer from progressive cognitive impairment in addition to other severe clinical manifestations. Standard enzyme replacement therapy does not result in sufficient brain concentrations to adequately address cognitive impairment.

DNL310 is a recombinant form of the IDS enzyme engineered to cross the blood-brain barrier using Denali’s proprietary enzyme transport vehicle technology. DNL310 is administered intravenously and intended to improve overall clinical manifestations of Hunter Syndrome, including neurological symptoms, which are not adequately addressed by currently approved therapies.

Denali’s transport vehicle technology enables improved uptake and distribution of therapeutic antibodies, enzymes, and other proteins in the brain after intravenous administration by binding to natural transport receptors in the vasculature of the brain. Preclinical studies have shown Denali’s transport vehicle technology results in up to a 30-fold increased uptake and superior pharmacological activity compared to standard antibodies, enzymes, and other proteins, the company said.

Denali is developing a broad portfolio of biologic drug candidates that are enabled by its technology. Based on pre-clinical proof of concept with DNL310, Denali initiated two additional enzyme replacement therapy programs using its technology.

Rare Pediatric Disease Designation is granted by the FDA in the case of serious or life-threatening diseases affecting fewer than 200,000 people in the United States and primarily in individuals 18 years of age and younger. The sponsor of a drug with rare pediatric disease designation may be eligible for a priority review voucher upon approval of the drug that can be used to obtain priority review of a subsequent marketing application.

The vouchers are potentially lucrative because they are transferable. In March, GW Pharmaceuticals sold its priority review voucher for $105 million. Past sales have ranged from $80 million to $350 million.

The FDA also granted Denali Orphan Drug designation for DNL310. The designation provides tax credits for clinical costs, exemptions from certain FDA fees, and seven years of marketing exclusivity if a marketing application is approved.

Denali expects to begin a phase 1/2 patient study of DNL310 in Hunter syndrome in 2020.

Ryan Watts, CEO of Denali, said the blood-brain barrier has been a major challenge for the development of therapeutics for neurodegenerative diseases. He believes the company’s technology provides a non-invasive solution to deliver higher concentrations and broader distribution of protein-based therapeutics in the brain and will improve treatments. “DNL310 is our most advanced program utilizing our TV platform,” he said, “and once in clinical testing, could provide human proof of concept for this approach.”

Photo: Ryan Watts, CEO of Denali

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