Denali Therapeutics advances ETV platform at WORLDSymposium 2026: tividenofusp alfa nears FDA approval for Hunter syndrome; progress in Sanfilippo MPS IIIA (DNL126) and Pompe (DNL952).
Written By: Nikita Jha BPharm
Reviewed By: Pharmacally Editorial Team
Denali Therapeutics presented clinical and preclinical data from its Enzyme Transport Vehicle (ETV) platform at the 22nd Annual WORLDSymposium in San Diego, advancing Hunter syndrome (MPS II), Sanfilippo type A (MPS IIIA), and Pompe disease by overcoming the blood-brain barrier for enzyme therapies targeting peripheral and CNS tissues.
Peter Chin, Acting Chief Medical Officer and Head of Development, said: “The data underscore strong progress for Denali’s ETV platform, supporting a potential tividenofusp alfa launch for Hunter syndrome while advancing Sanfilippo and Pompe programs via regulator and patient collaboration.”
Hunter Syndrome: Tividenofusp Alfa Nears FDA Decision
Hunter syndrome (MPS II) is a rare lysosomal storage disorder from iduronate-2-sulfatase deficiency, causing multi-organ damage and neurological decline.
Phase 1/2 data for tividenofusp alfa (DNL310) showed sustained CSF and urine heparan sulfate normalization over four years, with stabilization/improvement in cognition, adaptive behavior, hearing, and liver volume no new safety signals.
The BLA is under FDA Priority Review, targeting April 5, 2026. Approval would mark the first ERT for both neurological and systemic Hunter manifestations.
Sanfilippo Type A: Biomarker Wins for DNL126
Sanfilippo type A (MPS IIIA) features rapid neurocognitive decline from heparan sulfate buildup.
Phase 1/2 data for DNL126 showed CSF heparan sulfate/GM3 reductions, urine heparan sulfate drops, liver volume improvements, and CNS biomarker normalization in several patients.
FDA alignment on CSF heparan sulfate as a surrogate endpoint supports accelerated approval; BLA planned for 2027, with Phase 3 underway.
Pompe Disease: DNL952 Phase 1 Design
Pompe disease involves acid alpha-glucosidase deficiency, glycogen accumulation, and muscle weakness.
Phase 1 for DNL952 (ETV-enabled ERT) will assess safety, PK/PD in late-onset patients, including prior ERT users. Preclinicals showed superior skeletal muscle/brain glycogen clearance vs. existing therapies.
These programs highlight ETV’s potential to transform lysosomal and neuromuscular treatments.
About Denali’s Transport Vehicle™ Platform
The TV platform uses engineered Fc domains binding transferrin/CD98 receptors for IV delivery of biologics across the blood-brain barrier via transcytosis. Animal models show 10-30x higher brain exposure than standard biologics.
Elizabeth Jalazo, UNC Chapel Hill and Phase 1/2 investigator, stated: “DNL126’s early biomarker reductions are a key step for Sanfilippo type A, lacking disease-modifying options.”
References
Denali Therapeutics Presents Enzyme TransportVehicle™ Progress Across Three Clinical Programs for Treatment of Lysosomal Storage Disorders at 2026 WORLDSymposium™, 05 February 2026, Denali Therapeutics Presents Enzyme TransportVehicle™ Progress Across Three Clinical Programs for Treatment of Lysosomal Storage Disorders at 2026 WORLDSymposium™ | Denali Therapeutics