Company: DNLI
Filing Date: 2025-02-27
Form Type: 10-K
Source: 0001714899-25-000066
Chunk: 120

Company: Denali Therapeutics Inc.
Filing Date: 2025-02-27
Form: 10-K
Item: Item 1
Chunk 120
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 will include preclinical and clinical data on biomarkers (CSF and urine heparan sulfate and neurofilament light ("NfL")), safety data, and clinical data including liver volume, hearing thresholds, cognition, and adaptive behavior.

We are engaged in prelaunch activities including continued dialogue with prescribers and payers, building a suite of patient support services and capabilities to enable broad access. We are building a right-sized team in commercial and medical affairs to support tividenofusp alfa and additional ETV product launches. The ongoing open-label extension of the Phase 1/2 study will generate long-term safety data. We are also conducting the global Phase 2/3 COMPASS study, which will support global approval. 

The Phase 2/3 COMPASS study is being conducted in North America, South America, and Europe. The participants are randomized 2:1 to receive either tividenofusp alfa or idursulfase, respectively. Cohort A includes children ages ≥2 to <6 years with neuronopathic disease; cohort B includes children ages ≥6 to <26 without neuronopathic disease. Enrollment of the planned 33 participants with neuronopathic MPS II in Cohort A was achieved in late 2024, and we decided to increase the sample size of Cohort A by 9 participants, bringing the total to 42 participants. Cohort B continues to enroll participants with non-neuronopathic MPS II. 

We have previously reported interim analyses from the Phase 1/2 study and most recently reported the primary analysis of efficacy and safety at the 2025 WORLDSymposiumTM in February 2025. The Phase 1/2 study is a multicenter, multiregional, open-label, single-arm study to assess the safety, pharmacokinetics, and pharmacodynamics of tividenofusp alfa administered once weekly by intravenous infusion. The primary analysis included data from 47 participants who completed the 24-week treatment period and additional long-term follow-up. Long-term data demonstrated that robust reductions and normalization in key biomarkers from baseline were maintained over time with continued improvement in hearing, cognition and adaptive behavior. In addition, long-term safety data with median follow-up of two years, and out to more than four years, demonstrated that tividenofusp alfa was generally well tolerated. Key results are summarized below.

The primary efficacy and safety analysis reported at the 2025 WORLDSymposiumTM demonstrated that treatment with tividen