Denali Therapeutics Announces Decision to Advance DNL151 into Late Stage Clinical Studies in Parkinson’s Patients
DNL151 selected to advance into two late stage studies in Parkinson’s disease in patients with a kinase activating mutation in LRRK2 and in patients with sporadic disease
- Denali and collaboration partner Biogen are finalizing DNL151 clinical development plans and intend to commence patient enrollment in 2021
SOUTH SAN FRANCISCO, Calif., Aug. 06, 2020 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (NASDAQ: DNLI), a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (“BBB”) for treatment of neurodegenerative diseases, today announced that DNL151 has been selected to progress into late stage studies in Parkinson’s disease patients with a kinase activating mutation in LRRK2 and in sporadic Parkinson’s disease patients.
“Safety and biomarker data from studies of our two LRRK2 molecules in Parkinson’s patients support moving DNL151 into late stage clinical studies with the aim of addressing the devastating clinical decline and pathology of disease in Parkinson’s patients," said Carole Ho, M.D., Chief Medical Officer. “Our collaboration partner Biogen is a respected leader in neurodegenerative diseases and brings deep scientific and development expertise in Parkinson’s disease which will allow us to accelerate our development plan and we believe increase the likelihood of ultimate success.”
LRRK2 is a regulator of lysosomal function, which is impaired in Parkinson’s disease and may be restored by LRRK2 inhibition. Inhibition of LRRK2 activity may slow the progression of Parkinson’s disease in patients with and without known genetic risks based on restoration of lysosomal function. Mutations in the LRRK2 gene can cause Parkinson’s disease and are a major driver of lysosomal dysfunction, which contributes to neurodegeneration.
DNL151 has completed dosing of 162 healthy volunteers in an ongoing Phase 1 clinical study and 25 Parkinson’s patients in a Phase 1b clinical study. Denali is currently completing further dose escalation cohorts in an expanded Phase 1 and an additional cohort in the Phase 1b study to define the full therapeutic window of the molecule. Based on the clinical data to date that have been generated in Europe, DNL151 appears to have an acceptable safety and tolerability profile, and has met desired target engagement goals. An Investigational New Drug application for DNL151 was cleared by the U.S. Food and Drug Administration in July 2020 and enables expansion of our clinical studies for DNL151 globally. Based on the totality of preclinical and clinical data to date, both DNL201 and DNL151 (two chemically distinct LRRK2 inhibitors) have met Denali’s requirements to proceed into further late stage clinical studies. However, Denali has selected DNL151 due to pharmacokinetic properties that provide additional dosing regimen flexibility.