854 Bermekimab, anti-IL-1α antibody, inhibits skin injury induced response in healthy subjects

Interleukin-1 alpha (IL-1α) is constitutively expressed in epithelial cells located at barrier sites, such as skin, lung and gut. Upon cellular death, injury or infection, IL-1α released. Serum levels of are largely undetectable healthy volunteers (HV), atopic dermatitis (AD) hidradenitis suppurativa (HS) patients, while the especially epidermis exudates from HS tunnels, highly concentrated. Bermekimab (BMK) a first-in-class fully human anti-IL-1α monoclonal antibody that has been tested Ph2A AD & studies. To support understanding PK/PD relationships, we developed skin explant model to assess proteomic transcriptomic effects blockade on injury-induced inflammation. After 24-hours culture, was detected media. Ex vivo resulted significant decreases CXCL1, IL-8, GCSF IL-6 compared untreated samples (p<0.05 for all analytes), consistent reduction 73 genes (N=10 donors). Next, utilized this measure post-treatment PD HV receiving single dose BMK Ph1 study (NCT04544813). exhibited linear PK following IV (400-1200 mg) SC (200-800 administration. Consistent with ex blockade, were reduced culture media post-dose versus pre-dose explants significantly higher % IL-8 observed 800mg 200mg cohorts both analytes). Down-regulation same also observed. These data relevance key alarmin driving tissue inflammation, reduces downstream responses. Clinical research evaluating inflammatory diseases ongoing.