Company: DNLI
Filing Date: 2025-02-27
Form Type: 10-K
Source: 0001714899-25-000066
Chunk: 110

Company: Denali Therapeutics Inc.
Filing Date: 2025-02-27
Form: 10-K
Item: Item 1
Chunk 110
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 disease; and DNL343 (small molecule eIF2B activator) for amyotrophic lateral sclerosis (“ALS”). 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 and develop a new class of barrier-crossing therapeutics by leveraging our TV platforms and deep expertise in BBB biology to enhance the delivery of biotherapeutics to the brain and throughout the body.

2)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)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.

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We expect our first potential product launches will be with tividenofusp alfa for MPS II followed by DNL126 for MPS IIIA. MPS II and MPS IIIA belong to a group of lysosomal storage diseases, which are caused by genetic mutations that lead to single-enzyme deficiencies. Lysosomal storage diseases afflict more than 30,000 individuals worldwide. About two-thirds of these diseases affect the CNS; however, the current standard treatment, enzyme replacement therapy, does not address CNS manifestations, even for the lysosomal storage diseases where enzyme replacement therapy is available. Our ETV therapeutics are designed as next-generation enzyme replacement therapies to address both CNS and somatic manifestations of lysosomal storage diseases. Our planned BLA submission for tividenofusp alfa under the accelerated approval pathway is based on alignment with the FDA that cerebrospinal fluid ("CSF") heparan sulfate may be used as a surrogate biomarker for MPS II. Likewise, given that CSF heparan sulfate is also the primary substrate in MPS IIIA, we are seeking to align with the FDA on an accelerated approval path for DNL126. Together, we expect these two programs to be the foundation of a broad commercial franchise of ETV-enabled enzyme replacement therapies with a collective market potential of over $3 billion. 

 We are engaged in prelaunch activities for tividenofusp alfa including continued dialogue with prescribers and payers, building a suite of patient support services and capabilities to enable broad access, and building a right-sized team in