To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BT-267 in healthy adults (HA).

Leucine rich repeat kinase 2 (LRRK2) mutations are a well-known genetic cause of Parkinson’s disease (PD). Brains of individuals with idiopathic PD have increased LRRK2 kinase activity, which contributes to endolysosomal dysfunction and accumulation of ?-synuclein. Activation of LRRK2 kinase activity contributes to the pathogenesis of PD, suggesting inhibition of LRRK2 kinase activity may be useful for the treatment of PD.  BT-267 is a selective, brain-penetrant, oral small molecule inhibitor of LRRK2.

As of Oct 10, 2025, 40 participants were enrolled and completed dosing. BT-267 was well tolerated; no serious adverse events (AEs), withdrawals, or discontinuations were observed.  Most treatment emergent AEs were mild; only headache occurred in >2 participants. No clinically meaningful changes in vitals, labs, or electrocardiograms were observed. BT-267 exposure increased with dose and supports once-daily dosing. BT-267 CSF/plasma concentration ratio was > 1.6. Dose-dependent median reductions from baseline were observed in p/tLRRK2 ratio and p/tRab10 ratio.

BT-267 has preferential distribution in the central nervous system, with potential to maximize central exposures while minimizing peripheral exposures. These results suggest that BT-267 may provide a differentiated safety profile and support continued investigation of BT-267 in HA and individuals with PD.