Palisade's ulcerative colitis drug effective in mice, safe in dogs

Palisade Bio has recently released promising preclinical data on their PDE4 inhibitor, PALI-2108, aimed at treating ulcerative colitis, a chronic inflammatory bowel disease. By conducting studies on mouse models, the biotechnology firm has showcased the drug's potential efficacy and safety profile.

In a press release dated May 21, Palisade Bio revealed that PALI-2108, an oral prodrug, effectively mitigated symptoms of colitis in mice over an eight-day treatment period. Administered twice daily, the drug demonstrated a dose-dependent protection against typical colitis symptoms such as colon shortening, weight loss, and blood in the stool. This promising development underscores the therapeutic potential of PALI-2108, which operates by targeting the PDE4 enzyme family, key regulators of cytokine production involved in inflammatory processes.

The efficacy of PALI-2108 was compared to apremilast, another PDE4 inhibitor marketed under the name Otezla by Amgen, which has also been trialed for ulcerative colitis. The findings suggest that PALI-2108 engages its target with a similar effectiveness as apremilast.

At the annual Digestive Disease Week conference in Washington, D.C., Palisade Bio presented these findings in a poster, which also included data on the drug’s safety profile in dogs. The studies indicated that PALI-2108 is non-toxic to canines and possesses a broader therapeutic window compared to its metabolite, PALI-0008. Notably, no vomiting was observed in dogs even at higher doses of PALI-2108 (43-mg/kg), whereas lower doses of PALI-0008 (1-mg/kg and 3-mg/kg) did induce vomiting.

Dr. Mitch Jones, the Chief Medical Officer at Palisade Bio, expressed optimism regarding the study results, emphasizing that the data adds to the growing body of evidence supporting the potential of PALI-2108 in treating ulcerative colitis. PALI-2108 is being positioned as a lead candidate in a market valued at over $7 billion, which currently lacks highly effective treatments that do not also bring significant side effects. Unlike other PDE4 inhibitors approved for different conditions, PALI-2108 is specific to the colon and is activated by gut microbiota, which may result in fewer side effects compared to existing therapies.

Looking ahead, Palisade Bio plans to submit an Investigational New Drug (IND) application to the FDA by the fourth quarter of this year. Should this submission be successful, the company aims to initiate a first-in-human clinical trial in the first half of 2025. This timeline was detailed in an April presentation to investors, highlighting the company’s commitment to advancing PALI-2108 through the clinical development stages.

In summary, Palisade Bio's latest preclinical data on PALI-2108 offers encouraging insights into its potential as a safer and more effective treatment for ulcerative colitis. With plans to advance to human trials in the near future, PALI-2108 could eventually provide a much-needed alternative in the therapeutic landscape for this debilitating disease.