Denali Therapeutics (DNLI) FY2025 results: revenue $0

Denali Therapeutics discovers and develops biotherapeutics designed to reach the brain and the rest of the body. It built a proprietary delivery technology called the TransportVehicle ("TV") to carry large molecules across the blood-brain barrier after systemic administration. Its most advanced program, tividenofusp alfa for Hunter syndrome (MPS II), had a biologics license application under priority review by the United States Food and Drug Administration (FDA), with a target action date of 5 April 2026.

How the technology works

The TV is modular and can carry enzymes, oligonucleotides and antibodies. It engages the transferrin receptor ("TfR"), a natural transport route into the brain. Other approaches use the Fab portion of a full-length antibody to bind the receptor. Denali instead builds the binding site into the Fc domain. The company is also working on a second receptor, CD98hc, and on a dual platform that engages both TfR and CD98hc.

The technology is organised into franchises: Enzyme TV ("ETV"), Oligonucleotide TV ("OTV") and Antibody TV ("ATV"). The filing says more than 200 subjects have joined clinical studies of TV-enabled programs, and more than 11,000 doses have been given, for up to over five years, as of 3 November 2025.

What is in the pipeline

• Tividenofusp alfa (ETV:IDS) is for MPS II, which affects over 2,000 individuals in commercially accessible geographies. The global Phase 2/3 COMPASS study runs in North America, South America and Europe. Cohort A completed enrollment of 44 participants in December 2025. The FDA has granted Fast Track and Breakthrough Therapy designations.
• DNL126 (ETV:SGSH) is for Sanfilippo syndrome type A (MPS IIIA), for which the filing says there are no approved treatments. Its Phase 1/2 study enrolled 20 participants.
• TAK-594/DNL593 (PTV:PGRN) is for frontotemporal dementia caused by granulin mutations (FTD-GRN). Its Phase 1/2 study has enrolled 40 participants.
• DNL952 (ETV:GAA) is for Pompe disease. The FDA placed its Phase 1 application on clinical hold in December 2025 and lifted the hold in January 2026.
• Alzheimer's disease: DNL628 (OTV:MAPT) targets tau and is moving into a Phase 1b study. DNL921 (ATV:Abeta) targets amyloid.
• BIIB122/DNL151 is a small molecule LRRK2 inhibitor for Parkinson's disease that does not use the TV. Biogen runs the Phase 2b LUMA study, which enrolled 650 participants.

Its partners

• Biogen: The two companies co-develop and co-commercialise the LRRK2 inhibitors. Biogen funds 60% of development costs and Denali funds 40%. Profits and losses are shared equally in the United States. In China, Biogen takes 60% and Denali 40%. Biogen ended its license to the ATV:Abeta program in July 2024.
• Takeda: The two companies share development and commercialisation costs, and profits, for PTV:PGRN equally. Takeda leads commercialisation in the United States and China.
• Sanofi: Sanofi is solely responsible for developing eclitasertib, a peripherally restricted RIPK1 inhibitor, in ulcerative colitis. Denali is entitled to royalties.
• Genentech: Denali holds a license to Genentech's LRRK2 inhibitor program.
• Royalty Pharma: In December 2025 the two companies agreed a funding arrangement in exchange for a 9.25% royalty on future net sales of tividenofusp alfa. It is subject to closing conditions, including FDA accelerated approval on or before 30 June 2026.

Making and selling medicines

Denali relies on contract development and manufacturing organisations, including Lonza, for most clinical supply. Its own clinical biomanufacturing facility in Salt Lake City, Utah, opened in 2025. It uses standard antibody processes, including Chinese hamster ovary cell culture and Protein A affinity purification. The company says it expects to keep a hybrid approach that combines internal capability with outside manufacturers.

For tividenofusp alfa, the company has built United States marketing, distribution and sales capabilities. It is in discussions with possible regional partners for markets outside the United States. Its stated geographic focus is the United States and the European Union. For programs under the Takeda, Sanofi and Biogen agreements, it says it expects to commercialise only in certain geographies and to rely on partners elsewhere.

Who it competes with

The company lists efficacy, safety profile, method of administration, cost, level of promotional activity and intellectual property protection as the key competitive factors. Approved Alzheimer's therapies it names include LEQEMBI (Eisai and Biogen) and KISLUNA (Eli Lilly). In lysosomal storage diseases it names JCR Pharmaceuticals, RegenxBio, Kyowa Kirin and Orchard Therapeutics, and Ultragenyx. Companies developing competing blood-brain barrier delivery technologies include JCR Pharmaceuticals, Roche, Eli Lilly, AbbVie, Regeneron and Sanofi, among others.

How it protects its inventions

As of 31 December 2025, the owned and licensed patent portfolio included over 1,600 patents and patent applications. Of these, over 30 are licensed United States issued patents and 40 are owned United States issued patents. Denali owns 10 patent families on the TV platform, and the earliest are expected to expire in 2038. The company also relies on trademarks, trade secrets and know-how, and requires employees and consultants to sign confidentiality agreements.

From Denali Therapeutics's annual report on Form 10-K for the year ended 31 December 2025. The filing

Written from the 10-K filed 26 February 2026: read the full 10-K.