Denali Therapeutics Announces First Participant Dosed in Phase 2a Study of LRRK2 Inhibitor, BIIB122, in LRRK2-Associated Parkinson’s Disease

Denali Therapeutics Inc. recently announced initiation of dosing in a global Phase 2a clinical study, BEACON, of the investigational drug leucine-rich repeat kinase 2 (LRRK2) inhibitor BIIB122 (DNL151) in participants with LRRK2-associated Parkinson’s disease (LRRK2-PD). LRRK2 inhibition is a potential therapeutic approach that may slow progression of Parkinson’s disease by targeting underlying lysosomal dysfunction implicated in this disease.

The Phase 2a study is intended to evaluate safety and biomarkers associated with oral daily dosing of BIIB122 in approximately 50 participants with Parkinson’s disease and LRRK2 pathogenic mutations confirmed by genetic testing. The study is designed to enroll participants into a double-blind treatment period of three months followed by an open label extension. Denali holds the Investigational New Drug application for this Phase 2a study and is leading its design and execution. This study is being funded under a Collaboration and Development Funding Agreement between Denali and a third party. BIIB122 is also being investigated in the ongoing global Phase 2b LUMA study in participants with early-stage Parkinson’s disease with or without a LRRK2 mutation, in collaboration with Biogen.

“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,” said Carole Ho, MD, Chief Medical Officer at Denali. “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.”

“LRRK2 continues to be a prominent target in Parkinson’s research, and a priority area of focus for disease-modifying therapies,” added Todd Sherer, PhD, Chief Mission Officer of The Michael J. Fox Foundation. “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.”

Following discovery of the LRRK2 mutation as a pathogenic genetic factor for Parkinson’s disease, further research has uncovered that it has the potential to be a novel therapeutic target for Parkinson’s disease. Pathogenic mutations in LRRK2 account for 4-5% of familial and 1-2% of sporadic Parkinson’s disease.

BIIB122 (DNL151) is a selective, central nervous system-penetrant small molecule inhibitor of LRRK2 that is hypothesized to improve lysosomal dysfunction.

Denali’s strategic partner Biogen is 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. More information about the Phase 2b LUMA study (NCT05348785) can be found here.

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, which is defined as Parkinson’s disease in individuals who are heterozygous or homozygous carriers of a pathogenic LRRK2 variant that increases LRRK2 kinase activity. This study’s purpose is to evaluate the safety, tolerability, and pharmacodynamic effects of BIIB122. More information about the Phase 2a BEACON study (NCT06602193) can be found here.

BIIB122 is an investigational drug that is not approved by any regulatory authority, and its safety and efficacy have not been established.

Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier for neurodegenerative diseases and lysosomal storage diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the blood-brain barrier and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For additional information, visit www.denalitherapeutics.com.