Core Insights - Denali Therapeutics Inc. is poised for significant advancements in 2026, focusing on the launch of its first TV-enabled medicine, tividenofusp alfa, for Hunter syndrome, which is expected to set a new standard of care [2][4] - The company anticipates multiple clinical data readouts and plans to initiate clinical studies for Alzheimer's disease and Pompe disease, emphasizing its commitment to developing transformative medicines [2][7] Clinical Programs - **Tividenofusp alfa (DNL310, ETV:IDS)**: Denali is preparing for a commercial launch pending FDA's decision on the Biologics License Application (BLA) with a target action date of April 5, 2026. The Phase 1/2 trial results were published in The New England Journal of Medicine [4][5] - **DNL126 (ETV:SGSH)**: Initial clinical data from the ongoing Phase 1/2 study for Sanfilippo syndrome Type A will be presented at the 2026 WORLDSymposium [5] - **TAK-594/DNL593 (PTV:PGRN)**: The ongoing Phase 1/2 study for frontotemporal dementia is expected to yield initial patient data in 2026 [6] - **DNL628 (OTV:MAPT)**: This program targets Alzheimer's disease and is designed to cross the blood-brain barrier. The Phase 1b study has been approved and is set to begin [7][8] - **DNL952 (ETV:GAA)**: The FDA has lifted the clinical hold on this program for Pompe disease, allowing the Phase 1 study to proceed [9] - **BIIB122/DNL151**: The Phase 2b LUMA study for Parkinson's disease completed enrollment in 2025, with results expected in 2026 [10] Financial Outlook - As of September 30, 2025, Denali had approximately $872.9 million in cash and equivalents. In December 2025, the company completed an equity financing of about $200 million and entered a royalty funding agreement with Royalty Pharma, potentially yielding up to $275 million based on future sales of tividenofusp alfa [14] Key Anticipated 2026 Milestones - **Tividenofusp alfa**: Expected US Accelerated Approval in the first half of 2026 [15] - **DNL126**: Phase 1/2 data presentation in the first half of 2026 [15] - **DNL628**: Initiation of Phase 1b study in the first half of 2026 [15] - **DNL952**: Initiation of Phase 1 study in the first half of 2026 [15] - **DNL151/BIIB122**: Phase 2b LUMA data expected in the first half of 2026 [15] - **DNL126**: Phase 3 study initiation in the second half of 2026 [15] - **DNL593**: Phase 1/2 data expected in the second half of 2026 [15]

Denali's TransportVehicle (TV) Platform - Denali's TransportVehicle (TV) platform enables systemic delivery of biologics to the brain and other hard-to-target tissues[14, 25] - The company's TransportVehicle (TV) is the most clinically validated BBB technology with over 11,000 doses administered[61] - Denali's TransportVehicle (TV) platform has demonstrated best-in-class properties for brain uptake, modularity, safety, and architecture[55] Near-Term Launch Opportunities - Denali plans to launch tividenofusp alfa (DNL310) in 2026 and DNL126 in 2027, which could capture a $1B+ market opportunity[15] - Tividenofusp alfa has a PDUFA target action date of April 5, 2026[168] - Denali is targeting all ~2,000 MPS II patients worldwide in commercially accessible geographies[246] Pipeline and Therapeutic Areas - Denali has a broad clinical-stage pipeline across high-value therapeutic areas, including Alzheimer's disease and Parkinson's disease[16] - The company estimates a total addressable market (TAM) of >$5B for the ETV franchise[63] - Denali estimates a >$5B market potential for BBB-enabled AD therapeutics[68] Financial and Strategic Execution - Denali is well-capitalized and focused on efficient capital allocation and execution timelines for long-term value creation[17] - The company has secured $275M in potential total funding through a royalty financing agreement with Royalty Pharma[443] - Denali projects COGS <20% of revenue due to efficient processes[407]