RT Journal Article SR Electronic T1 Profiling the impact of two JAK inhibitors in a pre-clinical model of allergic asthma JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 3302 DO 10.1183/13993003.congress-2020.3302 VO 56 IS suppl 64 A1 James Pinkerton A1 Bilel Dekkak A1 Dimitrios Zervas A1 Thomais Markou A1 Annika Borde A1 Anders Cavallin A1 Therese Ericsson A1 Ramon Hendrickx A1 Ann Aurell Holmberg A1 John Steele A1 Maria Belvisi A1 Mark Birrell YR 2020 UL http://erj.ersjournals.com/content/56/suppl_64/3302.abstract AB Introduction: Asthma is a chronic inflammatory disease of the airways with typical symptoms manifesting in coughing, wheezing and dyspnoea. Whilst current treatments can be effective, some patients are not properly controlled, and the medications are not ideal and are associated with unwanted side effects. Thus, new therapies are urgently required. Typically, the chronic inflammation endotype is associated with increased levels of type 2 cytokine such as IL-4, IL-5, IL-9 & IL-13. These pro-inflammatory signalling pathways critically depend on Janus Kinase (JAK) I or II signal transduction, therefore the inhibition of JAK pathways represents a promising therapeutic target in asthma.Aims and Objectives: To assess the potential benefit of JAK inhibition using two structurally distinct inhibitors in a in vivo model system.Methods: Two JAK inhibitors, AZD4604 & AZD0449, were intratracheally dosed into sensitised Brown Norway rats one hour prior to aerosolised allergen (OVA) challenge. In one set of animals we assessed target engagement (TE) in the lung tissue by measuring levels of pSTATs. In a parallel set, we measured the Late Asthmatic Response (LAR) and lung inflammation.Results: Administration of both AZD4604 and AZD0449 resulted in dose related reduction of pSTAT3 and pSTAT5, indicating TE in the lung. Furthermore, AZD4604 & AZD0449 administration suppressed LAR and airway inflammation to a similar level to that achieved with the ICS comparator, budesonide.Conclusions: These data indicate that JAK inhibition may be of benefit to patients suffering from allergic asthma.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3302.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).