Denali and Takeda Open FTD-GRN Clinical Trial Site at UPenn

Denali Therapeutics and Takeda Pharmaceutical Company’s phase 1/2 clinical trial for FTD caused by GRN mutations is opening its first U.S.-based trial site at the University of Pennsylvania (UPenn). The multicenter study is evaluating the safety and tolerability of the drug DNL593 in people with and without FTD.

DNL593 Reintroduces Progranulin Through Intravenous Delivery In FTD-GRN, mutations of the GRN gene cause an impairment of the protein progranulin, which protects neurons in the brain. DNL593 was designed to address progranulin deficits by reintroducing it through an intravenous drip. The experimental drug uses a “protein transport vehicle,” a form of protein that moves others around, to help progranulin safely pass through the protective blood-brain barrier.

Data from preclinical studies of DNL593 showed that it improved progranulin uptake, the process by which cells absorb it from their surroundings. In mouse models, the drug prevented neurodegeneration and dysfunction of glial cells, which serve as the primary immune defense of the central nervous system.

Denali and Takeda began the phase 1/2 study in 2022 with the goal of enrolling 106 participants across the two halves of the study; before coming to the U.S., the trial operated in Europe, Brazil, and Turkey. The first study phase will evaluate single doses of DNL593 in adults without FTD; in the second phase people with FTD will receive multiple, increasingly larger doses (known as a “multiple ascending dose” phase).

Study Currently Recruiting Participants at UPenn Hospital The U.S trial site is at the Hospital of UPenn in Philadelphia and is currently recruiting participants who are diagnosed with FTD-GRN for the second phase of the trial.

The second phase is a “double-blind” study, where half of the participants receive a placebo, and the rest the experimental drug. After this phase is completed, Denali and Takeda will proceed with an 18-month “open-label extension,” where all participants will have the option to take the drug. The companies expect to conclude dosing and data collection by November 2025.