ARV-102 / Arvinas - LARVOL DELTA

ARV-102: Oral PROTAC LRRK2 degrader (Arvinas Press Release) - "Initiate Phase 1b clinical trial in patients with progressive supranuclear palsy (1H 2026); Present initial data from the multiple dose cohort of the Phase 1 clinical trial in patients with Parkinson’s disease (2026)."

P1 data • Parkinson's Disease • Progressive Supranuclear Palsy

In patients, treatment reduced levels of LRRK2 protein (Parkinson's News Today) - "The results, presented in the late-breaking abstract...showed that both doses of ARV-102 were well tolerated. Only mild side effects were seen, among them headache, diarrhea, and nausea, according to the researchers....Data showed that levels of ARV-102 increased in a dose-dependent manner in both the blood and CSF, demonstrating that it reached the brain in these Parkinson’s patients."

P1 data • Parkinson's Disease

Parkinson’s therapy ARV-102 able to reach brain, where needed: Study (Parkinson's News Today) - "In the volunteers taking part in the Phase 1 study, once-daily dosing with ARV-102 reduced biomarkers of damaged lysosomes, which are the structures that break down waste products — such as the misfolded alpha-synuclein protein that is a hallmark of Parkinson’s — in the body. The experimental therapy also reduced the inflammatory status of microglia, the brain’s resident immune cells."

P1 data • Parkinson's Disease

First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of ARV-102, a PROTAC LRRK2 Degrader, in Healthy Participants (MDS Congress 2025) - "At single (10–200 mg) and multiple (10–80 mg) doses, ARV-102 was well tolerated, orally bioavailable, and CNS-penetrant, and achieved substantial peripheral and central LRRK2 degradation and pathway engagement in healthy participants. Based on these findings, a phase 1 SAD/MAD study of ARV-102 was initiated in patients with Parkinson's disease."

Clinical • First-in-human • P1 data • PK/PD data • CNS Disorders • Movement Disorders • Parkinson's Disease • Progressive Supranuclear Palsy • LRRK2

First Clinical Trials of ARV-102, a PROTAC LRRK2 Degrader: Characterization of Pathway Engagement in Healthy Volunteers and Patients With Parkinson's Disease (MDS Congress 2025) - "Proteomic analyses using CSF from HVs treated with 80-mg doses of ARV-102 daily for 14 days (n=9) showed decreases (mean % of baseline) in lysosomal (78.5% cathepsin H, 71.4% GPNMB, and 78.5% granulin) and microglial (85.9% C1QTNF1, 84.8% ENTPD1, and 46.8% CD68) pathway markers known to be elevated in LRRK2 Parkinson's disease, indicating ARV-102 regulates pathways linking LRRK2 to neurodegenerative disease. In the phase 1 study, 19 pts with Parkinson's disease received a single dose of ARV-102 or placebo (50-mg cohort: n=12; 200-mg cohort: n=7). Median reductions in LRRK2 protein levels from baseline in PBMCs were -86% in the 50-mg cohort and -97% in the 200-mg cohort, consistent with dose-dependent peripheral LRRK2 degradation seen in HVs."

Clinical • Late-breaking abstract • CNS Disorders • Movement Disorders • Parkinson's Disease • CD68 • ENTPD1 • GPNMB • LRRK2

ARV-102, a PROteolysis TArgeting Chimera (PROTAC) leucine-rich repeat kinase 2 (LRRK2) degrader, modulates pathways associated with Parkinson’s disease and progressive supranuclear palsy (PSP): proteomic analyses of cerebrospinal fluid (CSF) from non-human primates (NHPs) and healthy volunteers (Neuroscience 2025) - "In conclusion, the oral, brain-penetrant PROTAC LRRK2 degrader ARV-102 induced changes in neurodegenerative disease-relevant pathways regulated by LRRK2 in healthy volunteers. A phase 1 study assessing ARV-102 safety and biomarker engagement in patients with Parkinson’s disease is ongoing."

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease • Progressive Supranuclear Palsy • C1Q • CD68 • CTSB • ENTPD1 • GPNMB • LRRK2

Lrrk2 degrader discovery: a high throughput direct-to-biology screening platform (Neuroscience 2025) - "Notably, ARV-102, a selective LRRK2 degrader developed by Arvinas, crosses the blood-brain barrier (BBB) and induces degradation of LRRK2 in the cerebral cortex following a single oral dose in mice carrying the G2019S LRRK2 mutation...In conclusion, D2B platform enables rapid synthesis and evaluation of PROTACs, demonstrating its utility in LRRK2 degrader discovery. The approach is scalable, efficient, and adaptable to other neurodegenerative disease targets, such as mutant huntingtin (mHTT) and GSK-3β, broadening its potential impact in CNS drug discovery."

CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2

Arvinas to Present Clinical Data for ARV-102, a PROTAC LRRK2 Degrader, at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (GlobeNewswire)

Clinical data • Parkinson's Disease

Arvinas Reports Second Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "ARV-102: Oral PROTAC LRRK2 degrader: Share final data from the SAD/MAD cohorts of the Phase 1 clinical trial in healthy volunteers (2H 2025). Share initial data from the SAD cohort of the ongoing Phase 1 clinical trial in patients with Parkinson’s disease (2H 2025). Initiate enrollment in the multiple dose cohort of the Phase 1 clinical trial in patients with Parkinson’s disease (2H 2025); present initial data from multiple dose cohort (2026). Initiate Phase 1b clinical trial in patients with progressive supranuclear palsy (1H 2026)."

Enrollment status • New P1 trial • P1 data • Parkinson's Disease • Progressive Supranuclear Palsy

Arvinas Presents First-in-Human Data for Investigational Oral PROTAC ARV-102 Demonstrating Blood-Brain Barrier Penetration, and Central and Peripheral LRRK2 Degradation (GlobeNewswire) - P1 | N=47 | 2024-516888-84-00 | Sponsor: Arvinas Operations Inc. | "Results...were shared in a presentation at the 2025 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2025)...At a single oral dose of at least 60 mg, and once daily repeated oral doses of at least 20 mg, ARV-102 achieved greater than 50% LRRK2 reduction in the CSF and greater than 90% LRRK2 reduction in the peripheral blood mononuclear cells (PBMCs), indicating substantial central and peripheral LRRK2 protein degradation...Of the 47 volunteers across all SAD dose levels, the primary treatment related adverse events were headache and fatigue...ARV-102 exhibited median maximum concentration (Tmax) 6 hours after oral administration...ARV-102 at single doses of greater than or equal to 30 mg induced greater than 50% decreases in peripheral phospho-Rab10T73, a LRRK2 substrate and biomarker for downstream LRRK2 activity; data for this endpoint in the MAD cohort is pending."

P1 data • Parkinson's Disease

Anticipated Upcoming Milestones and Expectations (GlobeNewswire) - "ARV-102: Oral PROTAC LRRK2 degrader: Present final data from the SAD/MAD cohorts of the Phase 1 clinical trial in healthy volunteers (2H 2025); Continue enrollment and present initial data from the SAD cohort of the ongoing Phase 1 clinical trial in patients with Parkinson’s disease (2H 2025); Initiate the MAD cohort of the Phase 1 clinical trial in patients with Parkinson’s disease (2H 2025)."

P1 data • Trial status • Parkinson's Disease

Investigational therapy ARV-102 now in Parkinson’s trial (Parkinson's News Today) - "Arvinas has begun a Phase 1 clinical trial to test its investigational therapy ARV-102 in people with Parkinson’s disease, with Phase 1 data in healthy adults showing it was safe and worked as expected....The study involving people with Parkinson’s (EUCT 2024-516888-84-00) was initiated at the end of 2024 and is still recruiting adults at a site in the Netherlands. Arvinas expects to present some data this year."

P1 data • Trial status • Parkinson's Disease

FIRST-IN-HUMAN STUDY TO ASSESS THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ARV-102, A PROTAC LRRK2 DEGRADER, IN HEALTHY MALES (ADPD 2025) - "Conclusions At single doses of 10–200 mg, ARV-102 was orally bioavailable, well tolerated, and achieved substantial peripheral LRRK2 protein degradation with evidence of CNS distribution and target engagement. This study supports continued investigation of ARV-102 in neurodegenerative diseases associated with LRRK2 dysfunction."

Clinical • P1 data • PK/PD data • CNS Disorders • Targeted Protein Degradation • LRRK2 • RAB10

Arvinas Announces Oral Presentation at 2025 International Conference on Alzheimer’s & Parkinson’s Diseases (GlobeNewswire) - "Arvinas...today announced that data from the first-in-human study evaluating single-ascending and multiple-ascending doses in healthy volunteers of ARV-102 will be presented at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD), April 1-5, 2025 in Vienna, Austria."

P1 data • Alzheimer's Disease • Parkinson's Disease

Arvinas Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "ARV-102: Oral PROTAC LRRK2 degrader: Present SAD data from the ongoing Phase 1 clinical trial in healthy volunteers in an oral session at the Alzheimer’s Disease/Parkinson’s Disease (AD/PD) conference in Vienna, Austria (April 1-4, 2025) demonstrating: Bioavailability and brain penetration with dose dependent exposure in cerebral spinal fluid (CSF); Degradation of LRRK2 in the periphery and CSF of healthy volunteers. Complete enrollment and present initial data from the ongoing SAD Phase 1 clinical trial in patients with PD in 2025; initiate MAD cohort in patients with PD in 2025."

P1 data • Alzheimer's Disease • Parkinson's Disease