Denali Therapeutics Takes Full Control Of DNL593 After Takeda Ends Collaboration, Plans To Advance Therapy For Frontotemporal Dementia

Denali Therapeutics Inc. announced that Takeda has decided to end its collaboration with Denali on the co-development and co-commercialization of DNL593 (PTV:PGRN). The decision was based on strategic considerations and is not related to the safety or efficacy of the therapy. DNL593 is an investigational progranulin replacement therapy that uses Denali’s Protein Transport Vehicle™ (PTV) to deliver progranulin across the blood-brain barrier to the brain for the treatment of frontotemporal dementia caused by progranulin mutations (FTD-GRN). Following the termination of the collaboration, Denali will take full control of DNL593 and its related intellectual property portfolio.

Ryan Watts, Ph.D., Chief Executive Officer of Denali Therapeutics, said that while the partnership with Takeda was highly valued, the company is pleased to regain full ownership of DNL593. He emphasized confidence in the scientific rationale and the data generated so far, and highlighted plans to continue advancing DNL593 independently. 

Denali expects to report results from the ongoing Phase 1/2 clinical trial by the end of 2026. Dr. Watts also noted that the Transport Vehicle platform, the first FDA-approved technology capable of crossing the blood-brain barrier, provides a strong foundation for developing therapies for neurodegenerative diseases like frontotemporal dementia, for which no treatments currently exist to slow disease progression.

The ongoing Phase 1/2 study of DNL593 has completed enrollment with 40 participants who have FTD-GRN. Results, including biomarker data, are expected by the end of 2026. Interim findings from Part A of the study in healthy volunteers showed dose-dependent increases in cerebrospinal fluid progranulin levels, demonstrating effective delivery of DNL593 to the brain. The therapy was generally well tolerated, and no significant safety concerns have been reported to date.