Phase 2 Failure: JNJ-5120/PIPE-307 for the Treatment of Major Depressive Disorder

Contineum Therapeutics today announced that the MOONLIGHT-1 trial evaluating the effect of JNJ-5120/PIPE-307 for the treatment of major depressive disorder (MDD) did not achieve its primary efficacy endpoint.

Investigators evaluated improvement from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at day 5 compared with placebo. Analyses of the data, including prespecified exploratory endpoints, are still ongoing. As to safety profile, JNJ-5120/PIPE-307 was well-tolerated with no new safety signals.

About JNJ-5120/PIPE-307

JNJ-5120/PIPE-307 is currently being developed by Johnson & Johnson under a global license and development agreement. Johnson & Johnson continues to evaluate the trial data, including data related to prespecified exploratory endpoints, and assess the totality and clinical relevance of the findings to inform next steps for JNJ-5120/PIPE-307.

The MOONLIGHT-1 Study

The phase 2, MOONLIGHT-1 study was a randomized, double-blind, multicenter, placebo-controlled, proof-of-concept trial evaluating the efficacy, safety, and tolerability of JNJ-5120/PIPE-307 as monotherapy in adult participants with MDD. Investigators randomly assigned 107 individuals with MDD to receive 1 of 2 JNJ-5120/PIPE-307 regimens or placebo.

Failure in Multiple Sclerosis and MDD

Johnson & Johnson acquired PIPE-307 from Pipeline Therapeutics back in 2023, paying $50 million upfront and committing up to $1 billion for global rights to the M1 receptor antagonist. Pipeline, now known as Contineum, had completed 2 phase 1 trials of JNJ-5120/PIPE-307. After Johnson & Johnson took over, they initiated midphase studies in both relapsing-remitting multiple sclerosis (MS) and MDD.

Back in November 2025, the MS trial also failed in phase 2, missing its primary efficacy endpoint.³

References

1. Contineum Therapeutics reports phase 2 results for JNJ-5120/PIPE-307 for the treatment of major depressive disorder. News release. September 14, 2026. Accessed September 15, 2026. https://www.businesswire.com/news/home/20260914716616/en/Contineum-Therapeutics-Reports-Phase-2-Results-for-JNJ-5120PIPE-307-for-the-Treatment-of-Major-Depressive-Disorder

2. Taylor NP. J&J’s Contineum-partnered depression drug flunks another phase 2 test. Fierce Biotech. September 15, 2026. Accessed September 15, 2026. https://www.fiercebiotech.com/biotech/jjs-contineum-partnered-asset-flunks-another-phase-2-test

3. Mason G. Contineum's J&J-partnered MS drug fails to improve vision in phase 2. Fierce Biotech. November 20, 2025. Accessed September 15, 2026. https://www.fiercebiotech.com/biotech/contineums-jj-partnered-ms-drug-fails-improve-vision-phase-2