Palisade Bio Chooses Dose for PALI-2108 Phase 1 Ulcerative Colitis Study

Palisade Bio, Inc., a biopharmaceutical firm listed on Nasdaq under the ticker PALI, has announced significant progress in the development of its leading drug candidate, PALI-2108. This drug, aimed at treating Ulcerative Colitis (UC), is set to enter Phase 1 clinical trials by the end of the year. PALI-2108 is an orally administered, colon-specific PDE4 inhibitor prodrug designed for UC patients.

Dr. Mitch Jones, the Chief Medical Officer of Palisade Bio, explained that to determine the Maximum Recommended Starting Dose (MRSD) for human trials, the company used various complementary scaling methods. These included integrating data from both intravenous (IV) and oral (PO) administrations of PALI-2108 across different species. By analyzing the total pharmacokinetic (PK) data, Palisade Bio has been able to gather information believed to be an accurate predictor of human exposure. This approach ensures a scientifically sound and safe starting dose for the upcoming clinical studies. Dr. Jones expressed satisfaction with the progress and anticipation for commencing the Phase 1 trial soon.

The company has conducted an extensive range of preclinical studies to establish the initial dose for PALI-2108 in its Phase 1 study. These studies included pharmacodynamic (PD) trials in mice, and PK trials in various species such as mice, rats, dogs, and monkeys. A series of in vitro experiments were also carried out to profile the drug's metabolism and pharmacokinetics (DMPK) characteristics. In addition, pivotal Good Laboratory Practice (GLP) safety and toxicology studies were completed to support this determination.

Comprehensive simulations were conducted for both single and multiple dose administrations. These simulations covered expected Phase 1 dosing levels and assessed both single and multiple daily doses. The results indicated that dosing regimens with minimal accumulation are safe and fall within the doses that showed maximal efficacy in animal models.

A robust human PK model was created by scaling preclinical PK parameters to predict human exposure. This model included both the PK of PALI-2108 and its active metabolite, PALI-0008, providing a strong basis for the Phase 1 trials.

Based on the modeling and simulations, Palisade Bio has determined a starting dose for healthy volunteers, incorporating several orders of magnitude safety margin. The dose levels and trial designs have been carefully selected to ensure patient safety while maximizing the potential therapeutic benefits of PALI-2108. The upcoming Phase 1 clinical trial will aim to evaluate the safety, tolerability, and PK of PALI-2108 in both healthy volunteers and UC patients, as well as PD in UC patients. Continuous monitoring and assessment will guide future dose escalation and therapeutic strategies.

Palisade Bio is dedicated to developing and advancing innovative therapeutics for patients with autoimmune, inflammatory, and fibrotic diseases. The company believes that its targeted approach with novel therapeutics will significantly transform the treatment landscape.