A new experimental drug called PALI-2108, developed by Palisade Bio, has shown promising results in early-stage clinical trials for treating ulcerative colitis. This drug belongs to a class of medicines called PDE4 inhibitors, which help reduce inflammation in the gut. Unlike existing PDE4 inhibitors that affect the whole body, PALI-2108 is designed to activate only in the colon and lower part of the small intestine, minimizing side effects in other areas.
In the latest phase 1a/b trials, researchers found that PALI-2108 delivers its active form (PALI-0008) directly to the colon, where it stays active for a full 24 hours after a single dose. Blood and tissue tests showed that the drug’s active form stays in the gut at levels high enough to block inflammation continuously. In fact, the drug reaches steady, effective levels in the colon within about 48 hours and remains stable for long periods.
The drug works by targeting key inflammation pathways in the colon, including JAK-STAT, NF-κB, TNF-α, and TGF-β, which are involved in ulcerative colitis. Importantly, these effects were seen only in the colon tissue, not in the bloodstream, which suggests the drug is highly targeted and may avoid systemic side effects. Tests also showed that PALI-2108 reduced markers of inflammation in the gut, such as decreased levels of a protein called PDE4B, increased levels of cAMP (a chemical that helps reduce inflammation), fewer lymphocytes (a type of immune cell), and lower levels of faecal calprotectin (a marker of gut inflammation). Tissue samples from the colon also showed improvements in inflammation and scarring.
Mitch Jones, President and Chief Medical Officer of Palisade Bio, stated, “These results show that PALI-2108 is designed to activate only in the gut, where it is needed, and stays active throughout the day. This makes it a promising option compared to current PDE4 inhibitors, which can cause side effects because they affect the whole body.”
In earlier trials, all patients showed improvement in their symptoms, and 40% of patients achieved remission. The new data further support the idea that PALI-2108 could be a next-generation treatment for inflammatory bowel disease, including ulcerative colitis. Researchers are encouraged by these findings and plan to continue developing the drug for future studies.