Anti-IL17A (aa 26-40) polyclonal antibody

AIMS To assess safety, pharmacokinetics (PK) and clinical efficacy of bimekizumab (formerly UCB4940), a novel humanized monoclonal antibody and dual inhibitor of interleukin (IL)-17A and IL-17F, in subjects with mild plaque psoriasis. METHODS Randomized, double-blind, first-in-human study of bimekizumab in 39 subjects who received single-dose intravenous bimekizumab (8-640 mg) or placebo (NCT02529956). RESULTS Bimekizumab demonstrated dose-proportional linear PK and was tolerated across the dose range assessed. No subject discontinued due to treatment-emergent adverse events and no severe adverse events were reported. Bimekizumab demonstrated fast onset of clinically-meaningful effects on skin of patients with mild psoriasis as early asWeek 2. Maximal improvements (100% or near 100% reductions from baseline) in all measures of disease activity were observed between Weeks 8-12 in subjects receiving 160-640 mg bimekizumab. The duration of effect at doses >= 160mg was evident up toWeeks 12-20 after a single intravenous dose, dependent on endpoint. CONCLUSIONS This is the first study to demonstrate the safety, tolerability and clinical efficacy of a dual IL-17A and IL-17F inhibitor, in subjects with mild psoriasis. Bimekizumab showed fast onset of clinically-meaningful efficacy by Week 2, with a maximal or near-maximal magnitude of response that was maintained up to studyWeeks 12-20. These findings support the continued clinical development of bimekizumab for diseases mediated by both IL-17A and IL-17F, including psoriasis.

Obesity is a serious public health problem worldwide and has been associated in epidemiological studies with a unique type of non-atopic asthma, although the causal association of asthma and obesity has certain criteria, such as the strength of association, consistency, specificity, temporality, biological gradient, coherence, analogy and experimentation; nevertheless, the biological plausibility of this association remains uncertain. Various mechanisms have been postulated, such as immunological, hormonal, mechanical, environmental, genetic and epigenetic mechanisms. Our hypothesis favours immunological mechanisms because some cytokines, such as tumour necrosis factor alpha (TNF-alpha) and interleukin (IL)-17A, are responsible for orchestrating low-grade systemic inflammation associated with obesity; however, these cytokines are regulated by epigenetic mechanisms, such as gene promoter methylation.