BenevolentAI Investor Day Presentation Deck

PDE10 inhibition: potential to normalise dysregulated mechanisms in IBD ● Macrophage M1 M2. Dendritic Cell INF-KB PGE₂ IL-12 IL-6 IL-18 IL-18 IL-23 TNF Th1 IFNY TNFO IL-2 ILC3 TIL-17A IL-22 Th17 IL-17A IL-17F IL-21 IL-22 IL-23 • Reduced inflammatory cytokine release from intestinal epithelia via NFkB(¹) Reduced tissue-resident macrophage activation (¹) Reduced intestinal inflammation PDE10 inhibition ↑ CGMP ↑ CAMP Sources: (1) Harmel-Laws et al PLoS One 2013: (2) Han et al PLoS One 2011; (3) Brenna et al Scand J Gastroenterol 2015 Images: Nettleford and Prabhu, Antioxidants 2018 (left); He et al. Int J Mol Sci 2020 (right) fluid Na* Nutrients action as pena claudins PAMR agent occludin MLCK Nutrients MLCK TNF • Improved TJ assembly via PKG/PKA-mediated pMLC(2) • Improved fluid/mucus homeostasis via PKG phosphorylation of intestinal CFTR (3) Improved barrier integrity Benevolent 59

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