Denali Therapeutics Presents Enzyme TransportVehicle™ Progress Across Three Clinical Programs for Treatment of Lysosomal Storage Disorders at 2026 WORLDSymposium™

Core Insights - Denali Therapeutics Inc. presented data on its Enzyme TransportVehicle™ (ETV) platform at the 22nd Annual WORLDSymposium™, showcasing its potential for delivering enzyme replacement therapies (ERT) for Hunter syndrome, Sanfilippo syndrome type A, and Pompe disease [1][2] Denali Therapeutics Overview - Denali is focused on developing biotherapeutics that can cross the blood-brain barrier using its proprietary TransportVehicle™ platform, aiming to address neurodegenerative and lysosomal storage diseases [19] Hunter Syndrome (MPS II) - Tividenofusp alfa (DNL310) showed significant reductions in cerebrospinal fluid heparan sulfate and urine heparan sulfate, with improvements in clinical endpoints maintained through Week 201 [3][6] - The Biologics License Application (BLA) for tividenofusp alfa is under Priority Review by the FDA, with a decision expected by April 5, 2026 [3][6] - A case study of two siblings with non-neuronopathic MPS II supports the therapy's potential to address the full disease spectrum [4] Sanfilippo Syndrome Type A (MPS IIIA) - DNL126 (ETV:SGSH) is fully enrolled in a Phase 1/2 study, showing an 80% mean reduction in cerebrospinal fluid heparan sulfate and an 83% reduction in urine heparan sulfate at Week 49 [5][8] - The FDA has indicated that cerebrospinal fluid heparan sulfate may serve as a surrogate endpoint for accelerated approval, with a BLA submission expected in 2027 [8][15] Pompe Disease - DNL952 (ETV:GAA) is in a Phase 1 clinical study designed to evaluate its safety and efficacy in late-onset Pompe disease, with preclinical data showing improved glycogen reduction compared to second-generation ERTs [9][17] - The study will assess various dose regimens and includes treatment-naïve patients [9] Regulatory and Developmental Progress - Denali is collaborating with regulatory authorities to advance its ETV platform and is preparing for the commercial launch of tividenofusp alfa [2][6] - The company is also planning a global Phase 3 confirmatory study for DNL126 [8][15]