Palisade Bio has reported positive outcomes from the Phase Ib open-label cohort of an ileocolonic-targeted PDE4 inhibitor, PALI-2108, in those with moderate-to-severe ulcerative colitis (UC).
The company also announced Phase Ia multiple ascending dose (MAD) cohort’s colon tissue pharmacokinetic (PK) data.
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The open-label, seven-day Phase Ib study demonstrated a 100% clinical response rate and significant improvements in biomarkers and histology.
It involved five subjects who were administered a titrated twice-a-day dosage of PALI-2108 (30mg).
Outcomes from the Phase Ib cohort included a mean decrease of 62.8% in the modified Mayo score, with one subject achieving clinical remission.
Additionally, four out of five subjects showed a decrease in faecal calprotectin, averaging a 70% reduction, and plasma hsCRP levels reduced by 15%.
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By GlobalDataHistological assessments also indicated improvements, with the Nancy Index, Robarts Histopathology Index, and Geboes Score showing reductions of 58%, 56%, and 36%, respectively.
Mechanistic studies further confirmed the therapy’s inhibition of PDE4 and immunomodulatory effects, as evidenced by increased tissue cAMP levels in four out of five patients, a 40% average decrease in tissue lymphocytes, and a 51% average reduction in PDE4B expression.
RNA sequencing data supported these findings, revealing the downregulation of fibrotic, inflammatory and CDx biomarkers from baseline to the end of the trial.
Complementing the Phase Ib results, the Phase Ia MAD cohort provided insights into the therapy’s PK in the colon tissue. The active metabolite of the PDE4 inhibitor, PALI-0008, was found to be detectable in the colon tissue up to 36 hours after dose, with steady-state trough concentrations surpassing the IC90 level and minimal accumulation.
The half-life of the therapy surpassed that of any known PDE4 inhibitor, suggesting sustained local activity and supporting a dosing regimen of once a day.
With these results, the company plans to conclude a Phase Ib trial in those with fibrostenotic Crohn’s disease by the second half of this year.
Palisade aims to use the data from its completed Phase Ia and Ib trials in UC, alongside the upcoming trial in fibrostenotic Crohn’s disease, to support a Phase II investigational new drug (IND) application and clinical protocols submission to the US Food and Drug Administration (FDA) in the first half of 2026.
Palisade Bio CEO JD Finley said: “These results represent a significant milestone for PALI-2108.
“The early clinical activity, targeted delivery, dose flexibility, the potential for once-daily oral dosing, and its favourable safety profile position PALI-2108 as a potentially best-in-class oral therapy for patients with UC.”
In 2023, Palisade initiated enrolment, dosing in a dose optimisation trial of LB1148, a broad-spectrum serine protease inhibitor designed to minimise intestinal damage.
