| Total Companies | 9 |
|---|
| Phase 2 | 3 |
|---|
| Phase 1 | 2 |
|---|
| Preclinical | 2 |
|---|
| Discovery | 2 |
|---|
Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of familial Parkinson's disease, accounting for approximately 5-10% of cases. The G2019S mutation alone accounts for roughly 5% of all PD cases. LRRK2 kinase inhibitors represent one of the most advanced disease-modifying therapeutic approaches for genetically-defined PD.
For detailed mechanism information, see LRRK2 Kinase Pathway in Parkinson's Disease and LRRK2 Inhibitors for Parkinson's Disease.
| Company |
Drug |
Mechanism |
Status |
Development Notes |
| Biogen/Denali |
BIIB122 (DNL151) |
LRRK2 inhibitor |
Phase 2b (LUMA trial) |
Partnership; globally enrolled |
| Neuron23 |
NEU-411 |
LRRK2 inhibitor |
Phase 2 (NEULARK trial) |
Precision medicine approach; LRRK2+ patients only |
| Vanqua Bio/Genentech |
G007-LK (VQVN-0001) |
LRRK2 inhibitor |
Phase 1/2 |
Collaboration with Genentech/Roche |
| Company |
Drug |
Mechanism |
Status |
| Novartis |
UNR161 |
LRRK2 inhibitor |
Phase 1 |
| Denali |
DNL343 |
LRRK2 inhibitor |
Phase 1 |
| Company |
Drug |
Mechanism |
Stage |
| Bristol-Myers Squibb |
BMS-986260 |
LRRK2 inhibitor |
Discovery |
| GSK |
GSK-123 |
LRRK2 inhibitor |
Preclinical |
| Biogen/Ionis |
BIIB132 |
LRRK2 ASO |
Phase 1 |
| Merck |
Undisclosed program |
LRRK2 inhibitor |
Discovery |
Program: BIIB122 (formerly DNL151) — co-developed with Denali Therapeutics
- Mechanism: ATP-competitive LRRK2 kinase inhibitor
- Status: Phase 2b LUMA trial enrolling
- Target engagement: Demonstrated dose-dependent pSer935-LRRK2 reduction
- Page: Biogen
Programs: DNL151 (BIIB122), DNL343
- Mechanism: LRRK2 kinase inhibition
- Status: BIIB122 in Phase 2b; DNL343 in Phase 1
- Partnerships: Biogen (BIIB122), Biogen/Ionis (BIIB132 ASO)
- Page: Denali Therapeutics
Program: NEU-411
- Mechanism: Brain-penetrant LRRK2 kinase inhibitor
- Status: Phase 2 (NEULARK trial, NCT06436589)
- Differentiator: Precision medicine — exclusively enrolling LRRK2 mutation carriers
- Funding: $96.5M Series D (2025)
- Page: Neuron23
Program: VQVN-0001 (G007-LK)
- Mechanism: Potent, selective, brain-penetrant LRRK2 inhibitor
- Status: Phase 1/2 with Genentech/Roche collaboration
- Differentiator: Next-generation chemistry; validated biomarker (pSer935-LRRK2)
- Page: Vanqua Bio
Program: G007-LK (in collaboration with Vanqua Bio)
- Mechanism: LRRK2 kinase inhibition
- Status: Collaborative development with Vanqua Bio
- Page: Genentech, Roche
Program: UNR161
- Mechanism: ATP-competitive LRRK2 inhibitor
- Status: Phase 1
- Page: Novartis
Program: BMS-986260
Program: GSK-123
- Mechanism: LRRK2 inhibitor
- Status: Preclinical
- Page: GSK
Program: Undisclosed LRRK2 program
- Mechanism: LRRK2 inhibitor
- Status: Discovery
- Page: Merck
¶ Competitive Landscape
The LRRK2 inhibitor field has evolved significantly since the first-generation inhibitors. Key differentiators include:
- Brain penetration: Critical for target engagement in the CNS
- Selectivity: Off-target kinase inhibition can cause adverse effects
- Biomarker development: pSer935-LRRK2 as validated pharmacodynamic marker
- Patient selection: LRRK2 mutation carriers vs. sporadic PD
- Combination approaches: LRRK2 + GBA1 or alpha-synuclein targeting
gantt
title LRRK2 Inhibitor Development Timeline
dateFormat YYYY
axisFormat %Y
section Phase 2b
BIIB122 (LUMA) :active, 2024, 2026
section Phase 2
NEU-411 (NEULARK) :active, 2025, 2027
section Phase 1
G007-LK :2025, 2026
UNR161 :2025, 2026
DNL343 :2025, 2026
BIIB132 (ASO) :2024, 2025
section Preclinical
GSK-123 :2025, 2027
BMS-986260 :2025, 2028