Poolbeg Pharma, an infectious disease-focused biopharmaceutical company, has announced data from the bacterial lipopolysaccharide (‘LPS’) human challenge trial for POLB 001, a viral strain agnostic, small molecule immunomodulator being developed to address the unmet medical need arising from severe influenza and other acute inflammatory conditions.
POLB 001 was shown to be safe and well tolerated and had a potent effect in systemic and localised inflammatory response in a dose dependent manner.
Trial design
A total of 36 healthy volunteers aged 18 to 55 were enrolled and completed the trial. Subjects treated with POLB 001 exhibited a marked reduction in multiple markers of systemic and localised inflammation compared with placebo.
p38 MAPK target engagement within circulating blood cells caused a substantial ablation of blood cytokines which are synonymous with cytokine release syndrome (‘CRS’) common in severe influenza, patients receiving CAR T cell treatment and other acute inflammatory conditions.
The typical LPS-induced rise in plasma cytokine levels (TNF-α, IL-6, and IL-8) decreased between 57-81% across all cytokines in subjects treated with 70 mg or 150 mg POLB 001 (all highly significant P values <0.0003).
Trial effects
POLB 001 was shown to have the following dose dependent effects:
- Blunted the LPS associated rise in heart rate across all dose groups (P<0.001)
- Reduced body temperature and C-reactive protein (‘CRP’) levels, a clinically used nonspecific marker of inflammation
- Target engagement causing a dose dependent reduction in p38 phosphorylation activation status in white blood cells
POLB 001 infiltration into inflamed tissues blocked localised cytokine release and reduced invasion of tissue damaging inflammatory cells as reflected by:
- Complete ablation of tissue damaging neutrophil accumulation within the inflamed tissue
- LPS-induced rise in intermediate monocytes (inflammatory mediators) was substantially lower in subjects treated with 70 mg or 150 mg POLB 001
- A highly significant reduction in TNF-α in subjects treated with 150 mg POLB 001 of 65.1% (P<0.0009)
Official comment
Jeremy Skillington, PhD, Chief Executive Officer at Poolbeg Pharma, said: “Together these data indicate POLB 001 reaches all cells and tissues where p38 MAPK is expressed, shutting down inflammation and silencing multiple aspects of overactivated inflammation unlike many anti-inflammatory drugs that target a single immune pathway.
“POLB 001 blocks inflammation both locally and systemically and in a manner that suggests efficacy in treating life-threatening infections such as severe influenza or the CRS associated with other acute inflammatory conditions. POLB 001 has the potential to be an effective treatment in a wide range of inflammatory syndromes that present serious and life-threatening complications for patients. Due to our parallel clinical programs with POLB 001 we are particularly excited that these results support continued clinical investigation in both indications, and that we can share this positive data with potential Pharma partners ahead of schedule.”
