Denali Therapeutics Inc. (Nasdaq: DNLI) has commenced dosing in the global Phase 2a BEACON study, evaluating BIIB122 (DNL151), an investigational leucine-rich repeat kinase 2 (LRRK2) inhibitor, in individuals with LRRK2-associated Parkinson’s disease. This trial marks a significant step in exploring disease-modifying therapies for Parkinson's, a condition affecting millions worldwide. The study aims to assess the safety and biomarker effects of BIIB122, potentially offering a new approach to slow disease progression by targeting underlying lysosomal dysfunction.
The Phase 2a BEACON study is a multicenter, randomized, 12-week double-blind, placebo-controlled, parallel-group study, followed by an open label extension in participants with LRRK2-PD. Approximately 50 participants with Parkinson's disease and confirmed LRRK2 pathogenic mutations, verified through genetic testing, will be enrolled. Participants will receive oral daily doses of BIIB122. The primary objectives include evaluating the safety, tolerability, and pharmacodynamic effects of BIIB122.
Targeting LRRK2 in Parkinson's Disease
Mutations in the LRRK2 gene are known to be a significant genetic factor in Parkinson's disease, accounting for 4-5% of familial and 1-2% of sporadic cases. BIIB122 is designed as a selective, central nervous system-penetrant small molecule inhibitor of LRRK2, hypothesized to improve lysosomal function, which is often impaired in Parkinson's. By inhibiting LRRK2, the drug aims to address a key underlying mechanism of the disease, potentially slowing its progression.
Collaboration and Concurrent Studies
Denali's strategic partner, Biogen, is also conducting the global Phase 2b LUMA study of BIIB122, which is expected to enroll approximately 640 participants with early-stage Parkinson’s disease, including eligible participants with LRRK2 mutations. This collaborative effort broadens the scope of BIIB122's investigation and increases the potential to address both genetic and sporadic forms of Parkinson's disease.
Expert Commentary
Carole Ho, M.D., Chief Medical Officer at Denali, stated, "We are thrilled to initiate this study and broaden our efforts in evaluating BIIB122 as a potential treatment for people living with Parkinson’s disease related to LRRK2 mutations. We look forward to continued collaboration with the Parkinson’s community as we aim to generate biomarker and safety data to inform how LRRK2 inhibition may have an impact on the course of this disease."
Todd Sherer, Ph.D., Chief Mission Officer of The Michael J. Fox Foundation, added, "LRRK2 continues to be a prominent target in Parkinson’s research, and a priority area of focus for disease-modifying therapies. The Phase 2a study of BIIB122 is a meaningful milestone in advancing the potential of LRRK2 as a therapeutic approach for people with Parkinson’s disease."
