Denali Therapeutics Reports $512.5 Million Net Loss for 2025, Submits BLA for Tividenofusp Alfa

Denali Therapeutics Inc. reported a net loss of $512.5 million for the year ended December 31, 2025, compared to a net loss of $422.8 million for the previous year. The increased loss was primarily driven by higher operating expenses, partially offset by a decrease in interest and other income. The company's cash, cash equivalents, and marketable securities totaled $966.2 million as of December 31, 2025. The company has not generated any revenue from product sales and does not expect to generate any revenue from product sales for the foreseeable future.

Research and development expenses for 2025 were $418.8 million, an increase of 6% compared to $396.4 million in 2024. This increase was primarily due to higher external expenses for TV programs, increased other research and development expenses related to the commencement of operations at the Salt Lake City manufacturing facility, and increased personnel-related expenses. These increases were partially offset by a decrease in external research and development expenses for small molecule programs. General and administrative expenses rose to $136.6 million in 2025, a 30% increase from $105.4 million in 2024, driven by headcount increases and activities associated with preparing for the potential commercial launch of tividenofusp alfa.

Strategic developments in 2025 included the submission of a Biologics License Application (BLA) for tividenofusp alfa to the FDA, which was accepted for priority review with a PDUFA target action date of April 5, 2026. The company also announced ongoing dialogue with the FDA related to the eligibility of tividenofusp alfa to receive a Rare Pediatric Disease Priority Review Voucher (“PRV”) upon approval. In addition, the company entered into a royalty funding agreement with Royalty Pharma for up to $275.0 million in funding in exchange for a royalty on future net sales of tividenofusp alfa, contingent upon FDA approval. The company also announced that the Clinical Trial Application ("CTA") for DNL628 (OTV:MAPT) to initiate a Phase 1b study in Alzheimer’s disease was approved and study start-up activities are underway.

Key operational developments included the completion of enrollment in the Phase 1/2 study of DNL126 for MPS IIIA and the submission of an Investigational New Drug (IND) application for DNL952 for Pompe disease, which was subsequently placed on clinical hold and then lifted. The company also commenced operations at its clinical biomanufacturing facility in Salt Lake City, Utah. Biogen completed enrollment in the Phase 2b LUMA study for BIIB122/DNL151 in Parkinson's disease, with data expected in 2026. Takeda delivered notice of its election to terminate the ATV:TREM2 program, which became effective in April 2025.

Denali's outlook includes a focus on the potential commercial launch of tividenofusp alfa, pending regulatory approval, and continued advancement of its clinical and preclinical pipeline. The company expects to initiate dosing in the Phase 1 clinical study of DNL952 in participants with LOPD and in the Phase 1b clinical study of DNL628 in participants with Alzheimer’s disease. Data from the Phase 2b LUMA study in early-stage Parkinson's disease is expected in mid-2026. The company believes its existing cash, cash equivalents, and marketable securities will be sufficient to fund projected operations for at least the next twelve months.