Company: DNLI
Filing Date: 2025-02-27
Form Type: 10-K
Source: 0001714899-25-000066
Chunk: 118

Company: Denali Therapeutics Inc.
Filing Date: 2025-02-27
Form: 10-K
Item: Item 1
Chunk 118
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 defined by the patient selection biomarkers.

We recognize the urgency for people living with neurodegenerative and lysosomal storage diseases to have effective treatment options. Biomarkers have successfully been used as primary clinical endpoints to secure a faster path to approval in indications such as ALS and Alzheimer’s disease. We are actively engaged in efforts, which include collaboration with our patient communities, advocacy groups and other drug developers, to press for more regulatory flexibility in using biomarker data as the basis for approval in disease indications where the unmet medical need is high and treatment options are few or non-existent. These efforts are in addition to ongoing discussions with health authorities regarding the potential use of validated biomarkers as primary clinical endpoints to support faster paths to approval for our product candidates. In September 2024, we announced the outcome of a successful meeting with the Center for Drug Evaluation and Research ("CDER") of the FDA providing a path to filing a BLA for accelerated approval and subsequent conversion to full approval for tividenofusp alfa for the treatment of MPS II. Agreement was reached that CSF heparan sulfate is reasonably likely to predict clinical benefit and can be used as a surrogate endpoint to support accelerated approval for tividenofusp alfa in MPS II. We intend to submit the BLA under the accelerated approval pathway in early 2025. CSF heparan sulfate is also the key disease biomarker for MPS IIIA (Sanfilippo syndrome), and we are seeking alignment with the FDA on an accelerated approval path for DNL126.

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Our Programs

We are developing a broad portfolio of targeted therapeutic candidates for neurodegenerative and lysosomal storage diseases with discovery efforts expanding into other serious disease areas (Figure 7). Our programs are at various stages of clinical and preclinical development. In addition to our current clinical development portfolio, we expect to advance one to two new molecule entities (“NMEs”) into clinical development over the next three years beginning in 2025. We discuss our most advanced programs in further detail below.

Figure 7: Our therapeutic portfolio is broad and diverse, spanning neurodegenerative diseases, lysosomal storage diseases, and other serious diseases that may be addressed by our TV platform for enabling and enhancing the delivery of biotherapeutics to target tissues. 

Clinical Programs

Tividenofusp alfa (DNL310, ETV:IDS) Enzyme Replacement Therapy Program for MPS II (Hunter Syndrome)

MPS II, also called Hunter syndrome, is a rare genetic disease that affects