Denali Therapeutics Begins Dosing in Phase 2a Study of BIIB122 for LRRK2-Linked Parkinson’s Disease

Denali Therapeutics Inc., headquartered in South San Francisco, California, has commenced dosing in the BEACON Phase 2a clinical trial, which is examining the efficacy of the investigational drug BIIB122 (DNL151). This study specifically targets participants with Parkinson’s disease associated with leucine-rich repeat kinase 2 (LRRK2) mutations. The therapeutic strategy of LRRK2 inhibition aims to slow the progression of Parkinson’s disease by addressing lysosomal dysfunction, a key factor implicated in the disease’s development.

The BEACON Phase 2a study focuses on evaluating the safety and biomarker responses to daily oral doses of BIIB122 in approximately 50 participants. These participants must have Parkinson’s disease with genetically confirmed LRRK2 mutations. The study involves an initial three-month double-blind treatment phase, followed by an open-label extension. Denali Therapeutics is responsible for the study's design and execution, with funding support from a collaboration and development agreement involving a third party.

Carole Ho, M.D., Chief Medical Officer at Denali, expressed enthusiasm about the launch of the BEACON study, emphasizing its significance in expanding research on BIIB122 as a potential treatment for Parkinson's disease related to LRRK2 mutations. Ho highlighted the partnership with the Parkinson’s community as essential in gathering data on biomarkers and safety to understand the impact of LRRK2 inhibition on the disease.

Todd Sherer, Ph.D., Chief Mission Officer of The Michael J. Fox Foundation, underscored the importance of LRRK2 as a target in Parkinson’s disease research. He noted that the Phase 2a study of BIIB122 represents a critical step toward developing disease-modifying therapies.

The LRRK2 mutation was identified as a genetic factor in Parkinson’s disease, revealing its potential as a new therapeutic target. Mutations in LRRK2 are responsible for 4-5% of familial Parkinson’s and 1-2% of sporadic cases. BIIB122 (DNL151) is a selective inhibitor of LRRK2 that can penetrate the central nervous system and is believed to improve lysosomal dysfunction.

Denali’s strategic partner, Biogen, is conducting the global Phase 2b LUMA study of BIIB122. This study aims to enroll about 640 participants with early-stage Parkinson’s disease, including individuals with LRRK2 mutations. The BEACON study, on the other hand, is a multicenter, randomized, 12-week, double-blind, placebo-controlled study followed by an open-label extension. It focuses on participants with LRRK2-associated Parkinson’s disease to assess the drug's safety, tolerability, and pharmacodynamic effects.

While BIIB122 remains an investigational drug and has not received approval from any regulatory authority, its safety and efficacy are yet to be established through ongoing clinical trials.

Denali Therapeutics, a biopharmaceutical company, is committed to developing treatments for neurodegenerative and lysosomal storage diseases by focusing on genetically validated targets and engineering drug delivery across the blood-brain barrier. Their approach involves rigorous assessment through biomarkers to ensure therapeutic engagement and effectiveness.

For more information about Denali Therapeutics and their clinical trials, further details can be explored on their official website.