Denali Therapeutics Announces Decision to Advance DNL151 into Late Stage Clinical Studies in Parkinson’s Patients - Seite 2

Denali and Biogen are working to finalize the clinical development plans for the LRRK2 program and intend to commence two separate Parkinson’s disease studies, one in patients with a kinase activating mutation in LRRK2 and the other in patients with sporadic disease. Patient enrollment is expected to commence in 2021.

About Denali’s LRRK2 program

Denali has two CNS-penetrant small molecules that inhibit LRRK2 in clinical studies, DNL201 and DNL151.

DNL 201 has successfully completed a Phase 1 study in 122 healthy volunteer subjects and a Phase 1b study in 28 Parkinson’s disease patients. DNL201 has been generally safe and well tolerated in doses tested and met all target engagement and biomarker goals. Based on this, DNL201 has met the bar for progression into further clinical studies.

DNL151 has successfully completed dosing of 162 healthy volunteers in an ongoing Phase 1 study in healthy volunteer subjects and completed dosing in 25 Parkinson’s disease patients in a Phase 1b clinical study. DNL151 met safety, target engagement and biomarker goals in the Phase 1 healthy volunteer study. Denali is currently completing further dose escalation cohorts in an expanded Phase 1 and Phase 1b study to define the full therapeutic window. Target and pathway engagement of greater than 50 percent and a dose-dependent reduction of BMP in urine of up to 50 percent were observed at clinically relevant doses in healthy volunteers. The DNL151 Phase 1b study (NCT04056689) in Parkinson’s disease patients is a 28-day, multicenter, randomized, placebo controlled, double-blind clinical trial in patients with mild-to-moderate Parkinson’s disease being conducted in the U.S. and Europe. Its purpose is to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, including target and pathway engagement biomarkers as well as certain exploratory clinical endpoints, after multiple oral doses of DNL151. To date, 25 patients have been enrolled in the study, and the protocol has been amended to expand the study with up to 10 additional patients. Both the Phase 1 healthy volunteer and Phase 1b Parkinson’s patient studies are anticipated to complete in 2020.