Palisade Bio, a biopharmaceutical company focused on autoimmune and inflammatory diseases, has advanced its Phase Ia/b clinical trial of PALI-2108 for ulcerative colitis (UC) into the multiple ascending dose (MAD) cohorts. This follows the successful completion of all five planned single ascending dose (SAD) cohorts.
The Phase Ia/b study is designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of PALI-2108 in both healthy volunteers and patients with UC. The transition to MAD cohorts marks a significant step in the development of this novel therapeutic agent.
Favorable Safety Profile in Single Ascending Dose Study
Preliminary data from the SAD portion of the trial, which evaluated doses ranging from 15 mg to 450 mg, indicated that PALI-2108 was well-tolerated across all dose levels. Notably, there were no treatment-related dose reductions, serious adverse events (SAEs), or treatment-related laboratory abnormalities observed. Treatment-emergent adverse events (TEAEs) were mild and occurred only at the highest dose of 450 mg. Furthermore, no electrocardiogram (EKG) abnormalities or other serious safety concerns were reported, underscoring the favorable safety profile of PALI-2108.
Pharmacokinetic Analysis Supports Targeted Drug Delivery
Pharmacokinetic (PK) analysis from the SAD portion of the study demonstrated the delayed-release and extended-release characteristics of PALI-2108. This ensures sustained, dose-dependent drug exposure with high local concentrations in the colon, a key feature for the targeted treatment of UC.
Management Commentary
"We are excited to move from the SAD to the MAD portion of our Phase 1a/b study of PALI-2108, a significant milestone that brings us one-step closer to delivering an innovative, safe, and effective treatment option for UC patients," said Dr. Mitch Jones, Chief Medical Officer of Palisade Bio. "The preliminary data from the SAD cohorts have reinforced our confidence in PALI-2108’s safety profile, and we remain on track to report topline data in the first half of 2025."
Study Objectives and Design
The primary aim of the Phase Ia/b study is to assess the therapy’s tolerability, PK, and safety in healthy volunteers, as well as its safety, tolerability, PK, and pharmacodynamics (PD) in UC subjects. PALI-2108 is a new chemical entity and a phosphodiesterase-4 (PDE4) inhibitor that has not been previously administered to humans.
To gain insights into the therapy’s effects, biomarkers such as serum high-sensitivity C-reactive protein (hsCRP) and fecal calprotectin will be used. Additionally, colonic tissue histological assessments will be performed to analyze drug and metabolite levels, PDE4 expression, cyclic adenosine monophosphate (cAMP) levels, absolute lymphocyte count (ALC), and related PD biomarkers, which are crucial for understanding the drug’s mechanism and efficacy.
