Takeda Terminates FTD Collaboration with Denali

Rare Daily Staff

Denali Therapeutics said Takeda has terminated their collaboration over Denali’s experimental frontotemporal dementia therapy, DNL593, and returned full rights to the program.

Takeda’s decision to end the partnership was driven by strategic considerations. The companies said the decision was unrelated to safety or efficacy concerns.

Denali will assume sole control over development and commercialization of DNL593, a progranulin replacement therapy designed to treat a rare genetic form of frontotemporal dementia known as FTD-GRN.

The company plans to continue clinical development of the therapy and expects results from an ongoing Phase 1/2 study by the end of 2026.

DNL593 uses Denali’s TransportVehicle technology, which is designed to ferry large therapeutic molecules across the blood-brain barrier, a longstanding obstacle in treating neurological diseases. The therapy aims to restore levels of progranulin, a protein deficient in patients with GRN gene mutations, one of the most common genetic causes of frontotemporal dementia.

Denali said its TransportVehicle platform has been clinically validated and is being used across multiple programs targeting neurodegenerative and other diseases.

The ongoing mid-stage study has enrolled 40 patients with FTD-GRN. Interim data from an earlier portion of the trial in healthy volunteers showed dose-dependent increases in cerebrospinal fluid progranulin levels, suggesting the drug reached the brain. The therapy has been generally well tolerated, with no significant safety signals reported to date.