Palisade Bio Selects Dose for Upcoming Phase 1 Clinical Study of PALI-2108 for Ulcerative Colitis

Palisade Bio, Inc. provided a progress update on the advancement of development for its lead drug candidate, PALI-2108 towards initiation of Phase 1 clinical trials in healthy volunteers and patients with Ulcerative Colitis (UC). PALI-2108 is an orally administered, locally acting colon-specific PDE4 inhibitor prodrug in development for patients affected by UC.

“To establish the Maximum Recommended Starting Dose (MRSD) for human trials, we utilized several complementary scaling approaches. These methods included integrating data from IV and oral (PO) administrations of PALI-2108 across various species. By modeling total PK data, we have gathered data that we believe accurately translates to exposure in humans and ensures a safe and scientifically grounded starting point for our upcoming planned clinical studies. We are pleased with the progress made and look forward to commencing our Phase 1 clinical trial before the end of the year,” said Dr. Mitch Jones, CMO of Palisade Bio.

The company has completed an extensive range of studies to determine the starting dose for PALI-2108 in its planned Phase 1 study. The preclinical studies included pharmacodynamic (PD) studies in mice, pharmacokinetic (PK) studies across multiple species (mice, rats, dogs, and monkeys), and a series of in vitro experiments to profile PALI-2108’s drug metabolism and pharmacokinetics (DMPK) characteristics. Additionally, the company has completed its pivotal Good Laboratory Practice (GLP) safety and toxicology studies which have provided relevant data for this determination.

Key Findings from PK Modeling and Simulations

• Comprehensive simulations were conducted for both single and multiple dose administrations. Scenarios ranged over expected Phase 1 dosing levels and assessed both single and multiple daily doses. The simulations indicated that dosing regimens with minimal accumulation are both safe and within the doses that demonstrated maximal efficacy in animal models.
• A robust human PK model was constructed by scaling preclinical PK parameters to predict human exposure. This model incorporated both the PK of PALI-2108 and its active metabolite, PALI-0008, providing a solid foundation for the Phase 1 trials.

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

Palisade Bio is a biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases. The company believes that by using a targeted approach with its novel therapeutics it will transform the treatment landscape. For more information, visit www.palisadebio.com.