Maurits Vissers (1987) was trained as a pharmacist at the University of Groningen. During this time he spent six months as a visiting researcher at the Massachusetts Institute of Technology, MA, USA. He held several positions within the industry in the fields of Pharmaceutical Manufacturing & Technology (Astellas), Pharmaceutical Compounding (Fagron) and Medical Affairs (AbbVie). He completed a Global Management Traineeship (Fagron) and High Performing Leadership Program (AbbVie). In 2018 he completed a post-graduate program on Clinical Development with the Paul Janssen Future Lab (Leiden). This program sparked an enthusiasm for Clinical Development and in 2018 Maurits joined CHDR as a Clinical Scientist to pursue a PhD in early phase clinical pharmacology studies with disease-modifying drugs for neurodegenerative disorders. In 2021, Maurits transitioned to the position of Experienced Clinical Scientist and in 2022 he completed training and registered as a Clinical Pharmacologist. Since 1 January 2023, Maurits holds the position of Clinical Operations Director and has joined CHDR’s Management Team.

Increased leucine-rich repeat kinase 2 (LRRK2) kinase activity is an established risk factor for Parkinson’s disease (PD), making LRRK2-kinase inhibition a promising therapeutic approach for slowing down disease progression. To try and develop a safe and effective treatment for PD, three early-stage clinical studies were conducted to translate preclinical discoveries into clinical applications using the potent, selective, CNS-penetrant LRRK2 inhibitor BIIB122 (DNL151). The first study aimed to characterize multiple LRRK2 pathway biomarkers, including total LRRK2 (tLRRK2), phosphorylation of Ser935 on LRRK2 (pS935), phosphorylation of threonine 73 on Rab10 (pRab10), and total Rab10 (tRab10), in different biological sources (whole blood, peripheral blood mononuclear cells [PBMCs], and neutrophils) as candidate human target engagement and pharmacodynamic biomarkers. The subsequent two phase 1 and phase 1b studies were randomized, double-blind, and placebo-controlled, involving a total of 186 healthy participants (146 randomized to BIIB122 and 40 randomized to placebo) and 36 patients with mild to moderate PD (26 randomized to BIIB122 and 10 randomized to placebo), respectively. Both studies found that BIIB122 was generally well tolerated, with a cerebrospinal fluid (CSF)-to-unbound plasma concentration ratio of approximately 1 (range, 0.7-1.8). Dose-dependent median reductions from baseline were observed in whole-blood pS935 (≤98%), PBMC pRab10 (≤93%), CSF tLRRK2 (≤50%), and urine bis (monoacylglycerol) phosphate (≤74%). These findings demonstrate substantial peripheral LRRK2 kinase inhibition and modulation of lysosomal pathways downstream of LRRK2, with evidence of CNS distribution and target inhibition by BIIB122. Overall, these results support continued investigation of LRRK2 inhibition with BIIB122 in (currently ongoing) late-stage phase 2 and 3 studies for the treatment of PD.