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GSK 165 (aGM-CSF): potential for a disease modifying effect in rheumatoid arthritis (RA) with a unique impact on pain gsk The target The agent - GM-CSF is a pro-inflammatory cytokine that induces differentiation and proliferation of granulocytes and macrophages One of the first cytokines detected in human synovial fluid from inflamed joints - Preclinical data suggests a broader range of actions than existing biologics (including a beneficial effect on pain) GSK'165 is a fully humanised antibody targeting anti-granulocyte macrophage colony-stimulating factor (aGM-CSF) Unmet need remains in RA despite development of new classes of agent (JAK inhibitors, anti IL6): ~50% of patients do not achieve low disease activity criteria within 12 months of aTNF treatment and ~80% do not achieve Disease Activity Score 28 (DAS28)1 Currently 45% of patients report daily pain despite treatment with targeted therapies and pain is the key driver in 25% of switches1 Semary nerve Current status Phase III started for RA in July 2019 Exploration of additional indications beyond RA Neutrophil Brain FLS GM-CSF GM-CSE INF GM CS IN GM-CSF MI toplaage Волепти Monocyte/ Macrophage MaDO IL:23 Blood Synovial joint vessel GM-CSF 1 Targeting GM-CSF in inflammatory diseases. Ian P. Wicks & Andrew W. Roberts. Nature Reviews Rheumatology volume 12, pages 37-48 (2016) 660

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