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]

Core Viewpoint - Denali Therapeutics Inc. is set to showcase its Enzyme TransportVehicle™ (ETV) programs at the 22nd Annual WORLDSymposium™, highlighting the potential of ETV in delivering enzyme replacement therapies throughout the body, including the brain [1]. Company Overview - Denali Therapeutics Inc. is a biotechnology company focused on developing biotherapeutics that can cross the blood-brain barrier using its proprietary TransportVehicle™ platform [2]. - The company has a clinically validated delivery platform and a diverse portfolio of therapeutic candidates at various stages of development, aiming to provide effective treatments for neurodegenerative diseases, lysosomal storage disorders, and other serious conditions [2].

Core Insights - Denali Therapeutics Inc. is set to present clinical and preclinical data from its Enzyme Transport Vehicle™ (ETV) programs at the 22nd Annual WORLDSymposium™ from February 2-6, 2026, showcasing the potential of ETV for delivering enzyme replacement therapies throughout the body, including the brain [1] Group 1: Clinical Data Presentations - Two oral presentations will cover follow-up data from the Phase 1/2 clinical study of tividenofusp alfa (DNL310) for Hunter syndrome (MPS II) and preliminary data from the ongoing Phase 1/2 study of DNL126 (ETV:SGSH) for Sanfilippo syndrome type A (MPS IIIA) [2][5] - The U.S. FDA is conducting a Priority Review of the Biologics License Application (BLA) for tividenofusp alfa, with a decision anticipated by April 5, 2026 [2] Group 2: Presentation Details - The platform presentations include a study on intravenous tividenofusp alfa for MPS II and preliminary results from the DNL126 study in children with MPS IIIA, both scheduled for February 5, 2026 [3] - Poster presentations will cover various topics, including a retrospective cohort study on unmet needs in Hunter syndrome, enhanced correction of skeletal muscle and brain pathology in a Pompe mouse model, and a case study involving a male sibling pair with MPS II [4][6] Group 3: Satellite Symposium - Denali will sponsor a satellite symposium titled "Transforming Patient Care in MPS II" on February 5, 2026, featuring expert speakers [7] Group 4: TransportVehicle™ Platform - Denali's TransportVehicle™ platform is designed to cross the blood-brain barrier, enabling the delivery of large therapeutic molecules, including antibodies and enzymes, to the brain, demonstrating significantly improved brain exposure compared to traditional methods [8] - The platform has been clinically validated, with five TV-enabled programs currently in clinical development [8] Group 5: Company Overview - Denali Therapeutics is a biotechnology company focused on developing biotherapeutics that can cross the blood-brain barrier, aiming to transform the lives of individuals with neurodegenerative and lysosomal storage diseases [9]