Denali Therapeutics Inc. reported financial results for the second quarter ended June 30, 2025, and provided business highlights. The company announced that the U.S. Food and Drug Administration (FDA) accepted its Biologics License Application (BLA) for tividenofusp alfa for Hunter syndrome (MPS II) for priority review, assigning a Prescription Drug User Fee Act (PDUFA) target action date of January 5, 2026. The BLA seeks accelerated approval based on data from a Phase 1/2 study, with tividenofusp alfa being an investigational enzyme replacement therapy designed to cross the blood-brain barrier (BBB) and deliver the iduronate-2-sulfatase (IDS) enzyme throughout the body and brain. The FDA previously granted the drug Breakthrough Therapy, Fast Track, Orphan Drug, and Rare Pediatric Disease designations. Denali continues to prepare for commercial launch and is conducting the Phase 2/3 COMPASS study to support global regulatory submissions.\n\nFor Sanfilippo syndrome Type A (MPS IIIA), Denali has reached alignment with the FDA’s Center for Drug Evaluation and Research (CDER) that cerebrospinal fluid heparan sulfate (CSF HS) may be considered a reasonably likely surrogate endpoint to predict clinical benefit and support accelerated approval of DNL126. Additional 49-week data from the ongoing open-label Phase 1/2 study are consistent with previously announced 25-week data, demonstrating a significant reduction in CSF HS from baseline, including normalization, and a favorable safety profile. Enrollment in the Phase 1/2 study is nearly complete, and planning is underway for a confirmatory global Phase 3 study.\n\nDenali and Takeda are continuing their collaboration to develop DNL593, an investigational therapeutic designed to deliver progranulin across the BBB for the treatment of granulin (GRN) mutation-associated frontotemporal dementia (FTD-GRN). A Phase 1/2 study is ongoing.\n\nDenali and Biogen are co-developing LRRK2 inhibitors for Parkinson’s disease. In May 2025, Biogen announced that the Phase 2b LUMA study of BIIB122 completed enrollment, with a readout expected in 2026. Denali is also conducting the Phase 2a BEACON study focused on LRRK2-associated PD.\n\nDenali expects to submit regulatory applications to begin clinical testing of one to two Transport Vehicle (TV)-enabled programs each year over the next three years across its Enzyme TV (ETV), Antibody TV (ATV), and Oligonucleotide TV (OTV) franchises. The most advanced programs include: DNL952 (ETV:GAA) for Pompe disease; DNL111 (ETV:GCase) for Parkinson’s/Gaucher disease; DNL622 (ETV:IDUA) for MPS I; DNL921 (ATV:Abeta) for Alzheimer’s disease; DNL628 (OTV:MAPT) for Alzheimer’s disease; and DNL422 (OTV:SNCA) for Parkinson’s disease.\n\nDenali announced the publication of preclinical data on ATV:Abeta in the August 7, 2025, issue of the journal Science. The research demonstrated that delivering an anti-amyloid beta antibody across the BBB using Denali's TV platform improved brain distribution and reduced the risk of amyloid-related imaging abnormality (ARIA) in a mouse model of Alzheimer’s disease, compared to conventional antibody treatment. The findings suggest that the TV platform enables brain delivery of immunotherapy by traveling through smaller capillaries, bypassing amyloid-laden large vessels, which offers a potential strategy to mitigate ARIA risk seen with first-generation anti-amyloid therapies.\n\nSecond Quarter 2025 Financial Results: Net loss was $124.1 million for the quarter ended June 30, 2025, compared to $99.0 million for the same period in 2024. Total research and development expenses were $102.7 million, up from $91.4 million in the prior year quarter, primarily due to increased spend on TV program external R&D and personnel-related expenses related to the commencement of operations at Denali's large molecule manufacturing facility in Salt Lake City, Utah. These increases were partially offset by a $9.8 million decrease in small molecule programs due to the winding down of activities related to the Phase 2/3 HEALEY ALS Platform Trial. General and administrative expenses were $32.3 million, up from $25.2 million, primarily driven by preparations for a potential commercial launch for tividenofusp alfa. Cash, cash equivalents, and marketable securities were approximately $977.4 million as of June 30, 2025.\n\nDenali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative diseases and lysosomal storage diseases. The company rigorously assesses genetically validated targets, engineers delivery across the BBB, and guides development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco and can be found at www.denalitherapeutics.com.\n\nThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include expectations regarding the TV platform and its therapeutics, timelines for regulatory approvals, commercial launch, clinical trial enrollment, and development of product candidates. All drugs currently being developed by Denali are investigational and have not received regulatory approval for any indication. Actual results may differ materially due to risks including adverse economic conditions, termination of agreements with collaborators, clinical trial enrollment challenges, manufacturing reliance on third parties, development risks, and regulatory uncertainties.

Denali Therapeutics Reports Second Quarter 2025 Financial Results and Business Highlights

Denali Therapeutics Inc. reported its second quarter 2025 financial results, noting a net loss of $124.1 million, up from $99.0 million in the same period of 2024. The company announced that the U.S. FDA accepted its Biologics License Application (BLA) for tividenofusp alfa in treating Hunter syndrome for priority review with a PDUFA target date of January 5, 2026. The drug, an enzyme replacement therapy designed to cross the blood-brain barrier, previously received Breakthrough Therapy, Fast Track, Orphan Drug, and Rare Pediatric Disease designations. Denali also reached alignment with the FDA on using cerebrospinal fluid heparan sulfate as a surrogate endpoint for Sanfilippo syndrome Type A, with ongoing Phase 1/2 data showing significant reduction in CSF HS and a favorable safety profile. The company continues Phase 2/3 COMPASS study and is planning a global Phase 3 trial. Denali is co-developing LRRK2 inhibitors with Biogen for Parkinson’s disease, with Biogen’s Phase 2b LUMA study completing enrollment and a readout expected in 2026. Denali is also conducting its Phase 2a BEACON study. The company plans to submit regulatory applications for one to two Transport Vehicle (TV)-enabled programs annually over the next three years, including candidates for Pompe disease, Parkinson’s, Gaucher disease, MPS I, Alzheimer’s, and frontotemporal dementia. Preclinical data on ATV:Abeta was published in Science, showing improved brain delivery and reduced ARIA risk in a mouse model of Alzheimer’s. Denali is based in South San Francisco and is developing therapies to treat neurodegenerative and lysosomal storage diseases.