Company: DNLI
Filing Date: 2025-02-27
Form Type: 10-K
Source: 0001714899-25-000066
Chunk: 112

Company: Denali Therapeutics Inc.
Filing Date: 2025-02-27
Form: 10-K
Item: Item 1
Chunk 112
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 for neurodegenerative and lysosomal storage diseases, we have a robust discovery effort to further expand our portfolio and capture the full potential of our TV platform to enhance delivery of biotherapeutics to all tissues in the body. We are pursuing opportunities of unmet need in multiple disease areas including oncology, inflammation, neuromuscular disease, and metabolic disease. For example, we have engineered a bispecific ATV:HER2 antibody and have demonstrated preclinically improved peripheral anti-tumor activity as well as enhanced brain uptake of the bispecific ATV:HER2 as compared to a non-ATV HER2 antibody. The data support the potential for ATV:HER2 to treat HER2-positive peripheral tumors and brain metastases and further validate the potential for TV applications in oncology. 

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Our therapeutic portfolio also includes two late-stage clinical programs for small molecule drug candidates that do not use the TV platform but are engineered with optimized chemical and physical properties to cross the BBB. Denali has an active collaboration with Biogen Inc.’s subsidiaries, Biogen MA Inc. (“BIMA”) and Biogen International GmbH (“BIG”) (BIMA and BIG, collectively, “Biogen”) for the development and commercialization of BIIB122/DNL151 (small molecule LRRK2 inhibitor) for Parkinson's disease. Biogen is conducting the global Phase 2b LUMA study, which is evaluating the ability of BIIB122 to slow disease progression as compared to placebo in approximately 640 participants with early-stage Parkinson's disease; completion of enrollment is expected in 2025. In addition, Denali is conducting the complementary Phase 2a BEACON study in LRRK2-associated Parkinson's disease with the aim to generate biomarker and safety data to inform how LRRK2 inhibition may impact this disease. Our small molecule eIF2B activator, DNL343, is being evaluated in Regimen G of the Phase 2/3 HEALEY ALS Platform Trial for amyotrophic lateral sclerosis ("ALS") led by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital ("MGH") in collaboration with the Northeast ALS Consortium ("NEALS"). Following previously reported topline results that the primary and key secondary endpoints were not met, further analyses are anticipated later in 2025, including neurofilament light ("NfL") and other fluid biomarkers, data from pre-specified subgroups, as well as extended findings from the active treatment extension period.

Collaborations