J&J has faced a setback in its collaboration with Contineum after their MS drug failed to show visual improvement in a mid-stage trial. Contineum Therapeutics’ M1 receptor antagonist has come up short in a phase 2 test of its impact on vision in patients with a common form of multiple sclerosis.
The Johnson & Johnson-partnered candidate, PIPE-307, did not produce a statistically significant improvement in binocular 2.5% low-contrast letter acuity in any treatment group, the San Diego-based company said after markets closed on November 20. As a result, the study failed to meet its primary efficacy endpoint and likewise missed its secondary efficacy goals.
The phase 2, double-blind, placebo-controlled trial included 182 people with relapsing-remitting multiple sclerosis, a form of the disease frequently linked to visual impairment, and tested two different dose levels of PIPE-307.
The trial showed that PIPE-307 was generally safe and well-tolerated at both doses, Contineum said. The company plans to dig deeper into the exploratory endpoints from the study and intends to present the full data at an upcoming medical meeting, followed by publication in a peer-reviewed journal.
Analysts at William Blair described the miss as disappointing but not unexpected, noting they had always viewed the trial as high risk. They pointed to previously mixed results seen with the H1 histamine blocker clemastine on the same low-contrast visual acuity measure in multiple sclerosis patients.
Contineum Chief Medical Officer and Development Lead Timothy Watkins said in a Thursday press release that the company plans to draw lessons from these results and remains dedicated to developing new treatments for patients with inflammatory and fibrotic conditions.
Contineum is advancing PIPE-307 through a collaboration with Johnson & Johnson. In 2023, J&J’s Janssen unit struck a licensing agreement for the oral MS candidate that included $50 million upfront and the potential for up to $1 billion in biobucks.
Beyond multiple sclerosis, Johnson & Johnson is running a phase 2 study of PIPE-307 in major depressive disorder.
William Blair wrote in a November 20 note that they view the RRMS data as offering limited insight into how PIPE-307 might perform in major depressive disorder, while acknowledging that the MDD program itself is still high risk – a view reflected in their 35% estimated probability of success for PIPE-307 in that indication. They attributed this to the challenging nature of placebo-controlled MDD trials, where strong placebo effects can decrease observed treatment differences and variability among patients can make response rates on active therapy more unpredictable.
J&J’s study’s topline information is expected to be available somewhere around the middle of the upcoming year. As far as Contineum goes, William Blair added that, in its view, most of Contineum’s value still lies in advancing its LPAR1 blocker PIPE-791 for idiopathic pulmonary fibrosis (IPF).
As the companies reassess the direction of PIPE-307, industry observers note that the collaboration between Contineum and J&J will likely remain focused on understanding whether the drug’s mechanism can offer benefits outside of vision-related outcomes. Several neurologists have pointed out that MS trials centered on visual endpoints are notoriously difficult, as individual variability in contrast sensitivity can dilute measurable improvements.
Still, the safety profile observed in the trial may give J&J enough confidence to continue exploring the compound in other neurological and psychiatric disorders where M1 receptor modulation could play a meaningful role.
For Contineum, the outcome serves as a reminder of the complexities involved in treating diseases driven by inflammation and demyelination, yet the company’s continued investment in innovative targets, alongside its partnership with J&J, suggests that it remains committed to addressing unmet needs across both neurodegenerative and fibrotic conditions.
Looking ahead, analysts believe the next major catalyst for both Contineum and J&J will be the release of topline data from the ongoing phase 2 trial in major depressive disorder. Although the indication carries its own challenges, particularly the high placebo response that often obscures drug effects, positive findings could help revive confidence in the broader M1 receptor program.
