Palisade Bio has released further phase 1a/b analyses of its investigational PDE4 inhibitor prodrug PALI‑2108, adding new evidence of colon‑targeted delivery, sustained active‑metabolite exposure and pharmacologic activity consistent with once‑daily dosing.
The company reported delayed ileocolonic activation, high tissue‑to‑plasma exposure and steady‑state concentrations of the active metabolite PALI‑0008 that remained above IC90 throughout the dosing interval.
These data build on earlier results showing rapid improvements across clinical, histologic and biomarker measures in ulcerative colitis.
According to Palisade, steady‑state analyses showed pre‑dose trough concentrations of PALI‑0008 exceeded the IC90 threshold and were around 20 percent higher than single‑dose Cmax, indicating continuous target inhibition.
The metabolite reached steady state within roughly 48 hours and demonstrated an extended half‑life. Tissue‑to‑plasma ratios of about six‑fold supported preferential localisation of drug activity to the intestinal mucosa.
Treatment with PALI‑2108 produced colon‑selective suppression of inflammatory and fibrotic pathways, including JAK–STAT, NF‑κB, TNF‑α and TGF‑β signalling.
These transcriptional effects were observed in colonic tissue but not peripheral blood. Biomarker changes aligned with PDE4 inhibition, including decreased mucosal PDE4B expression, increased cAMP, reductions in lymphocytes and marked decreases in faecal calprotectin. Histological improvements were also seen across multiple indices.
Mitch Jones, President and Chief Medical Officer of Palisade Bio, said: “These additional pharmacokinetic and translational analyses further characterise the differentiated profile of PALI‑2108, which is designed to be selectively bioactivated in the ileum and colon.
“We are encouraged by the sustained steady-state trough levels of the active metabolite, PALI-0008, relative to the IC90 threshold, with trough levels exceeding IC90 throughout the dosing interval, a profile that compares favorably to currently approved systemic PDE4 inhibitors.”
Previously reported phase 1a/b data showed consistent pharmacodynamic activity and clinical benefit, with all patients achieving clinical response and 40% achieving clinical remission. Palisade said the accumulating evidence supports continued development of PALI‑2108 as a next‑generation PDE4 inhibitor for inflammatory bowel disease.
