Business Description

Overview and Strategy Our purpose is to bring the power of biotherapeutics to the whole body, including the brain, by discovering, developing, and delivering medicines for people living with serious diseases. Historically, the blood-brain barrier has been a major challenge to the development of medicines for diseases of the central nervous system. While the blood-brain barrier protects the brain and is essential for our survival, it also prevents the delivery of medicines to the brain in sufficient quantities to have therapeutic effect. We have invented, developed, and validated a proprietary technology, called the TransportVehicle TM ("TV"), to address the blood-brain barrier challenge and enable a new class of barrier-crossing therapeutics. The TV has a modular design enabling delivery of large molecules, i.e., enzymes, oligonucleotides, and antibodies, to all tissues of the body, including the brain, by crossing the blood-brain barrier after systemic administration. Over the last few decades, large molecule biotherapeutics have enabled medical breakthroughs in treating a wide array of serious diseases, but with very limited success in central nervous system diseases. Now, with the invention and validation of our TV technology, we are leading the field in delivering on the potential of biotherapeutics to transform the lives of individuals with neurodegenerative diseases, lysosomal storage disorders, and other serious diseases. We are building a broad portfolio of therapeutic candidates by investing in our TV franchises, i.e., Enzyme TV ("ETV"), Oligonucleotide TV ("OTV"), and Antibody TV ("ATV"), to advance programs for rare diseases, such as lysosomal storage diseases, and common diseases, such as Alzheimer's disease and Parkinson's disease. Our most advanced TV-enabled program is tividenofusp alfa (DNL310, ETV:IDS) for the potential treatment of mucopolysaccharidosis II (" MPS II ", or Hunter syndrome ). The biologics license application ("BLA") for tividenofusp alfa is under priority review for accelerated approval by the U.S. Food and Drug Administration ("FDA"), and we have established commercial readiness in anticipation of the Prescription Drug User Fee Act (PDUFA) target action date of April 5, 2026. Our TV-enabled clinical development portfolio also includes DNL126 (ETV:SGSH) for mucopolysaccharidosis IIIA (“MPS IIIA”, or Sanfilippo syndrome type A), DNL593 (PTV:PGRN) for frontotemporal dementia-granulin (“FTD- GRN ”), DNL628 (OTV:MAPT) for Alzheimer’s disease, and DNL952 (ETV:GAA) for Pompe disease. We believe the combination of a clinically-validated delivery platform and a maturing therapeutic portfolio will position us for long-term success in our goal to deliver barrier-crossing, targeted, and effective medicines. Key elements of our strategy include: 1) Discover: Advance a new class of barrier-crossing therapeutics by leveraging our TV platforms and deep expertise in blood-brain barrier biology to enhance the delivery of biotherapeutics to the brain and throughout the body. 2) Develop: Accelerate and expand a broad portfolio of TV-based product candidates to fully unlock the potential of barrier-crossing therapeutics, applying patient-informed development and driving biomarker-guided regulatory approvals. 3) Deliver: Launch initial products targeting rare lysosomal storage diseases as a strategic foundation for expansion into common neurodegenerative conditions and other serious diseases, while building integrated capabilities for long-term growth and profitability. 6 Table of Contents Our “D3X3” strategy reflects our next phase of execution and is anchored in our “Discover, Develop, Deliver” (D3) framework, with three-year objectives (X3) across our portfolio, as we transition from platform validation to delivery and scalable growth. Our goals are to (i) deliver two growing commercial brands, tividenofusp alfa (ETV:IDS) for Hunter syndrome and DNL126 (ETV:SGSH) for Sanfilippo syndrome type A, establishing the foundation for a durable rare disease franchise; (ii) achieve five clinical proof-of-concept readouts across our portfolio, including programs in Alzheimer’s disease (ATV:Abeta and OTV:MAPT), FTD- GRN (PTV:PGRN), Pompe disease (ETV:GAA), and Parkinson’s disease (LRRK2 inhibitor); and (iii) advance four to six additional TV-enabled programs into the clinic ( Figure 1) .…