DNL151 / Denali Therap, Biogen - LARVOL DELTA

Results from a Phase 2b, Placebo-Controlled Study to Determine the Efficacy and Safety of BIIB122/DNL151 in Participants with Early-Stage Parkinson's Disease (MDS Congress 2026) - No abstract available

Clinical • Late-breaking abstract • P2b data • CNS Disorders • Movement Disorders • Parkinson's Disease

Baseline assessment of nigrostriatal integrity via VMAT2 PET in participants with Parkinson’s disease from the BIIB122/DNL151 LUMA Phase 2b study (MDS Congress 2026) - No abstract available

P2b data • CNS Disorders • Movement Disorders • Parkinson's Disease

Therapeutics candidates and repurposing strategies to target parkinson's disease pathology: current evidence and future directions. (PubMed, Metab Brain Dis) - "For proteostatic dysfunction, the USP14 inhibitor IU1 enhanced both proteasomal and autophagic flux, though neurotoxicity above 200 µM limits its therapeutic window; BIIB122, a selective LRRK2 inhibitor, achieved CNS target engagement in Phase 1/2 trials, but its Phase 3 LIGHTHOUSE study was terminated, with Phase 2b LUMA ongoing. In dopaminergic neurodegeneration, GLP-1 receptor agonists produced divergent outcomes: Exenatide-PD3 (n = 231) showed no benefit over placebo, whereas LixiPark demonstrated reduced motor progression in early-stage PD, revealing that mechanistic equivalence does not guarantee clinical equivalence across heterogeneous patient populations...Repurposed compounds, including ambroxol, N-acetylcysteine, doxycycline, metformin, and GLP-1 receptor agonists, demonstrate engagement with disease-relevant mechanisms and, in several cases, preliminary evidence of clinical activity...Future priorities must include: (i) precision stratification by..."

Journal • Review • CNS Disorders • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease • GBA • IL1B • LRRK2 • MMP3 • MMP9 • TNFA • USP14

Biogen and Denali Therapeutics Provide Update on Phase 2b LUMA Study of BIIB122 (DNL151) in Early-Stage Parkinson’s Disease (GlobeNewswire) - "Results from the study show that BIIB122 did not slow the progression of Parkinson’s disease versus placebo, as measured by the primary endpoint of Time to Confirmed Worsening in the modified Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II and III combined score. Secondary endpoints also did not show a benefit with BIIB122. Exploratory biomarker endpoints demonstrated >90% kinase inhibition of peripheral LRRK2 (phosphoserine 935) and, in a cerebrospinal fluid (CSF) sub-study, up to approximately 30% reduction observed in a biomarker of LRRK2 activity (phosphorylated Rab10). Expected levels of BIIB122 in the blood and CSF were sustained across the study....Based on these results, Biogen and Denali will discontinue further development of BIIB122 in idiopathic Parkinson’s disease."

Discontinued • P2b data • Parkinson's Disease

Smartphone-based digital assessments in the LUMA trial of BIIB122/DNL151 for early-stage Parkinson’s disease (WPC 2026) - P2 | "The protocol for Konectom assessments allows for a good compromise between feasibility and burden to the patients and enables the selection of digital endpoints based on test-retest reliability, relationship to established anchor measures of PD severity, and sensitivity to longitudinal progression. The digital data will allow for a comparison of performance in the clinic setting versus the free-living environment, provide insight into week-by-week variability in motor function, and may provide real-world, objective evidence of treatment efficacy in early-stage PD. Previously presented at MDS 2025."

CNS Disorders • Movement Disorders • Parkinson's Disease

LUMA: A Study to Learn About the Safety of BIIB122 Tablets and Whether They Can Slow the Worsening of Early-Stage Parkinson's Disease in Adults Between the Ages of 30 and 80 (clinicaltrials.gov) - P2 | N=650 | Completed | Sponsor: Biogen | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

Safety and Pharmacodynamic Effects of BIIB122 in Participants With LRRK2-Associated Parkinson's Disease (LRRK2-PD) (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Denali Therapeutics Inc. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Apr 2026 ➔ Mar 2027

Enrollment closed • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2

The global Phase 2a BEACON study is designed to assess safety, pharmacokinetics and biomarkers of lysosomal pathway engagement, which will inform the biomarker profile in LRRK2 pathogenic variant carriers and the impact of LRRK2 inhibition. (GlobeNewswire) - "Data from the BEACON study is anticipated in the first half of 2027. The BEACON study is being operationalized by Denali and funded under a Collaboration and Development Funding Agreement between Denali and a third party."

P2a data • Parkinson's Disease

BIIB122/DNL151 (small molecule LRRK2 inhibitor) for Parkinson’s disease (GlobeNewswire) - "A clinical data readout of the global Phase 2b LUMA study of BIIB122 for early-stage Parkinson’s disease is expected in mid-2026."

P2b data • Parkinson's Disease

Smartphone Typing Metrics Show High Reliability as Digital End Points in Phase 2b LUMA Study of BIIB122 (NeurologyLive) - "In an analysis of baseline data from 200 patients with PD, sensor-derived measures showed high reliability across in-clinic and remote assessment pairs, with 93% of measure combinations achieving an intraclass correlation coefficient (ICC) of 0.70 or greater and 53% demonstrating a minimal detectable change at the 95% confidence interval (MDC95%) of 0.2 or less. Results showed that Reaction Time (ICC, 0.60-0.81; MDC95%, 0.17-0.26), Letter Interval (ICC, 0.66-0.86; MDC95%, 0.18-0.28), and Number of Correct Words (ICC, 0.71-0.84; MDC95%, 0.22-0.29) showed the highest reliability....In the current analysis, presented at the 2026 AD/PD International Conference...the Konectom smartphone application assessment battery, which includes an active typing task (copying words), was evaluated as an exploratory end point."

P2b data • Parkinson's Disease

SMARTPHONE-BASED MEASUREMENT OF KEYSTROKE DYNAMICS IN THE PHASE 2B LUMA TRIAL IN PARKINSON'S DISEASE (ADPD 2026) - "In the LUMA Phase 2b study of BIIB122/DNL151, a Konectom smartphone application assessment battery, including an active typing task (Copying Words), is integrated as an exploratory outcome... Konectom's smartphone-based typing test provided reliable SDMs, capturing multiple dimensions of keystroke dynamics, hence promising to assess motor and nonmotor function during an ADL in PD. Further work will evaluate the sensitivity to disease progression relative to clinical anchors. Exploratory outcomes from the typing task may complement other ADL measures in LUMA."

P2b data • CNS Disorders • Movement Disorders • Parkinson's Disease

BIIB122/DNL151 (small molecule LRRK2 inhibitor) for Parkinson’s disease (Yahoo Finance) - "A clinical data readout of the global Phase 2b LUMA study of BIIB122 for early-stage Parkinson’s disease is expected in mid-2026."

P2b data • Parkinson's Disease

BIIB122/DNL151 (small molecule LRRK2 inhibitor) for Parkinson’s disease (GlobeNewswire) - "The global Phase 2b LUMA study of BIIB122...clinical readout expected in 2026. Denali’s Phase 2a BEACON study in LRRK2-associated Parkinson’s disease remains ongoing."

P2b data • Trial status • Parkinson's Disease

EVALUATION OF CENTRAL AND PERIPHERAL PATHWAY BIOMARKER RELATIONSHIPS IN RESPONSE TO LRRK2 KINASE INHIBITION BY BIIB122/DNL151 TREATMENT (ADPD 2026) - P2 | "Despite the limited sample size, similar dose response trends were observed in urine BMP and CSF pRab10 with BIIB122/DNL151 treatment. These data provide evidence that urine BMP may serve as a readily accessible biomarker of central effects of LRRK2 kinase inhibition at therapeutically relevant doses of BIIB122/DNL151. LUMA (NCT05348785), a Phase 2b trial evaluating LRRK2 inhibition with BIIB122/DNL151 in individuals with PD, has a larger sample size and longer treatment paradigm that will enable validation of this finding."

Biomarker • Parkinson's Disease • LRRK2

BIIB122/DNL151 (small molecule LRRK2 inhibitor) for the treatment of Parkinson’s disease (GlobeNewswire) - " The Phase 2b LUMA study completed enrollment earlier this year with a data readout expected in 2026, while Denali’s Phase 2a BEACON study in LRRK2-associated Parkinson's disease remains ongoing."

P2b data • Trial status • Parkinson's Disease

Smartphone-based digital assessments in the LUMA trial of BIIB122 for early-stage Parkinson's disease (MDS Congress 2025) - P2 | "The smartphone assessment protocol allows for a good compromise between feasibility and burden to the patients and enables the selection of digital endpoints based on test-retest reliability, relationship to established anchor measures of PD severity, and sensitivity to longitudinal progression. The digital data will allow for a comparison of performance in the clinic setting versus the free-living environment, provide insight into week-by-week variability in motor function, and may provide real-world, objective evidence of treatment efficacy in early-stage PD."

CNS Disorders • Movement Disorders • Parkinson's Disease

Phase 1 and 1b Pharmacodynamic Data Support Central Modulation of Lysosomal Pathways With BIIB122/DNL151, a LRRK2 Kinase Inhibitor: Insights for the LUMA Trial (MDS Congress 2025) - P1, P1b, P2 | "Despite the limited sample sizes, these data provide evidence that BIIB122 modulates LRRK2 pathways in the CNS at therapeutically relevant doses. Further analyses will evaluate the relationship of pRab10 alterations and other changes in lysosomal proteins. LUMA (NCT05348785), a Phase 2b trial evaluating LRRK2 inhibition in individuals with PD, will measure clinical progression and biomarker assessments to understand the overall impact of chronic LRRK2 inhibition in PD."

P1 data • PK/PD data • CNS Disorders • CTSS • LRRK2 • RAB10

Evaluation of the Pharmacodynamic Effects of BIIB122/DNL151 in Participants with LRRK2 mutation-driven Parkinson's disease (BEACON Study) (MDS Congress 2025) - P2 | "Data generated from this study will enable scientific insights into mechanisms and biomarkers of LRRK2-driven PD, deepen our understanding of the therapeutic mechanism of action of BIIB122/DNL151, and may reveal unique SAA+ versus SAA- LRRK2-PD biomarker signatures."

PK/PD data • CNS Disorders • Movement Disorders • Parkinson's Disease • CSF P-tau • LRRK2

BIIB122/DNL151 (small molecule LRRK2 inhibitor) for the treatment of Parkinson’s disease (PD) (GlobeNewswire) - "Denali and Biogen are jointly developing LRRK2 small molecule inhibitors for Parkinson’s disease (PD), with Biogen leading the global Phase 2b LUMA study evaluating the effect of BIIB122 on disease progression in early-stage PD. In May 2025, Biogen announced the Phase 2b LUMA study was fully enrolled with a readout expected in 2026."

P2b data • Parkinson's Disease

LUMA: A Study to Learn About the Safety of BIIB122 Tablets and Whether They Can Slow the Worsening of Early-Stage Parkinson's Disease in Adults Between the Ages of 30 and 80 (clinicaltrials.gov) - P2 | N=650 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Movement Disorders • Parkinson's Disease

HOW THE THERAPEUTIC APPROACH TO EARLY PARKINSON'S DISEASE WILL CHANGE IN THE NEXT FUTURE (ADPD 2025) - "Levodopa remains the most efficacious drug, a better preparation of levodopa like IPX 203 can ensure more stable plasma levels of Levodopa...Tavapadon is a new dopamine agonist stimulating D1-D5 receptors which concluded the phase III. Other compounds such as CVN424 (Cerevance) orally active and selective GPR6 inverse agonist, piperamat (IRLAB 752) a cortical enhancer to improve balance, Clenbuterol/Nadolol for cognition, mesdopetam a D3 antagonist are under investigation...These include the monoclonal antibody prasinezumab, UCB0599 and buntanetap small-molecules α-synuclein aggregation inhibitor, the vaccine ACI-7104.056 by AC immune...The LRKK2 kinase inhibitor BIIB122/DNL151 is in phase IIb in PD. BIAL BIA 28-6156 activator of the GCase enzyme is under investigation in patients with GBA mutation. The combination of symptomatic and disease modifying therapy, the use of accurate biomarkers and more precise treatment will be the future in the treatment of PD."

CNS Disorders • Movement Disorders • Parkinson's Disease • GBA

RESPONSE OF CSF LYSOSOMAL PATHWAY BIOMARKERS TO BIIB122/DNL151 TREATMENT IN PH1 AND PH1B CLINICAL TRIALS (ADPD 2025) - P1, P1b | "The pharmacodynamic Results suggest that BIIB122/DNL151 treatment centrally modulates levels of lysosomal pathway proteins in PD patients, a finding requiring confirmation in a treatment study with greater participant numbers and longer treatment duration. In addition to lysosomal pathway modulation, GPNMB and CTSS pharmacodynamic responses may reflect modulation of neuroinflammation, a pathway similarly implicated in PD pathogenesis."

Biomarker • Clinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • CTSD • CTSS • GPNMB

BIIB122/DNL151 (small molecule LRRK2 inhibitor) for the treatment of Parkinson’s disease (PD) (GlobeNewswire) - "Denali and Biogen have a strategic collaboration to jointly develop and commercialize small molecule inhibitors of LRRK2. Biogen is conducting the global Phase 2b LUMA study, which is evaluating the ability of BIIB122 to slow disease progression as compared to placebo in approximately 640 participants with early-stage Parkinson's disease; completion of enrollment is expected in 2025."

Enrollment closed • CNS Disorders • Parkinson's Disease

Denali Therapeutics Announces First Participant Dosed in Phase 2a Study of LRRK2 Inhibitor, BIIB122, in LRRK2-Associated Parkinson’s Disease (GlobeNewswire) - "Denali Therapeutics Inc...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)...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."

Trial status • CNS Disorders • Parkinson's Disease

Safety and Pharmacodynamic Effects of BIIB122 in Participants With LRRK2-Associated Parkinson's Disease (LRRK2-PD) (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Denali Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Parkinson's Disease