Palisade's ulcerative colitis drug prevents symptoms in mice, is nontoxic in dogs

Palisade Bio’s PDE4 inhibitor to treat the inflammatory bowel disease ulcerative colitis appears to be effective in mice, according to new data.

Twice-daily doses of Palisade's oral prodrug PALI-2108 for eight days protected mouse models of colitis from developing symptoms like shortened colons, weight loss and blood in the stool in a dose-dependent manner, the biotech explained in a May 21 press release.

The drug engaged its target as well as another PDE4 inhibitor, apremilast—commercialized by Amgen as Otezla—a psoriasis drug that has also been previously tested as an ulcerative colitis treatment.

Palisade presented the mouse studies as a poster (PDF) during the annual Digestive Disease Week conference in Washington, D.C., along with data showing that PALI-2108 was nontoxic in dogs and has a larger therapeutic window than the compound it metabolizes to, PALI-0008.

The researchers didn't see any vomiting in the animals following a single 43-mg/kg dose of PALI-2108, in contrast with just 1-mg/kg and 3-mg/kg doses of PALI-0008, according to dataon the poster.

“The findings from this preclinical study add to our growing body of encouraging data for PALI-2108 and further bolster our confidence in its potential in the treatment of [ulcerative colitis],” Mitch Jones, M.D., Ph.D., chief medical officer at Palisade, said in the press release. 

PALI-2108 is Palisade’s lead product candidate for ulcerative colitis, an estimated $7 billion-plus market that hosts many therapies but few that are effective or don’t come with side effects. It works by tamping down the activity of the enzyme family PDE4, which controls production of cytokines and is implicated in various inflammatory diseases. PALI-2108 is specific to the colon, unlike the PDE4 inhibitors approved for other conditions, and is converted into its active form by microbiota in the gut. This may make it less likely than other therapies to cause side effects.

Palisade expects to submit an IND application with the FDA by the fourth quarter of the year and launch a first-in-human trial in the first half of 2025, according to an April presentation (PDF) to investors.