LRRK2 has been a hotly pursued drug target for Parkinson’s Disease based on human genetics. Clinical advancement of LRRK2 inhibitors was initially stalled by concerns about on-target lung findings in primates, but these were ameliorated by a Merck/Genentech/Pfizer/MJFF study showing that these lung changes were reversible, and Biogen/Denali has currently a small molecule (BIIB122/DNL151) in Ph. II (NCT05348785) after demonstrating safety and CNS exposure in 145 healthy patients in Ph. I (NCT04557800). On Sunday, it was disclosed that additional, likely on-target adverse findings were observed in a primate GLP study on long-term treatment with Merck’s second-generation LRRK2 inhibitors.
Initial Detection of A Distinct Toxicity Related to LRRK2 Inhibition
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