Johnson & Johnson's muscarinic M1 receptor antagonist PIPE-307 (JNJ-5120) failed to separate from placebo in a Phase II depression trial, Contineum Therapeutics (Nasdaq: CTNM) reported on September 14.
The MOONLIGHT-1 trial — a randomized, double-blind, placebo-controlled, multicenter proof-of-concept study in adults with MDD — did not meet its primary endpoint of improvement from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Day 5. The drug was reported to be well-tolerated with no new safety signals. Johnson & Johnson said it is continuing to evaluate the data, including prespecified exploratory endpoints, to determine next steps.
PIPE-307 selectively blocks the muscarinic M1 receptor, a cholinergic target implicated in cognitive and mood regulation. The rationale for M1 antagonism in depression draws on evidence that excess cholinergic tone contributes to depressive states.
The MDD failure follows a separate Phase II setback for PIPE-307 in relapsing-remitting multiple sclerosis, where the VISTA trial missed its prespecified primary and secondary efficacy endpoints in 2025. Johnson & Johnson holds exclusive worldwide development and commercialization rights to the molecule under a 2023 deal, with sole discretion over further development in MDD, multiple sclerosis, or other indications. Contineum's wholly owned pipeline remains centered on PIPE-791, an LPA1 receptor antagonist in development for idiopathic pulmonary fibrosis and chronic pain.
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