BenevolentAI Investor Presentation Deck
PDE10 inhibition: potential to normalise dysregulated
mechanisms in IBD
Macrophage
M₂
M1
Dendritic Cell
INF-KB
PGE₂
IL-12
IL-6
IL-18
IL-1B
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)
Na Nutrients
ptir myn
ಬ
MLCK
PAMR
fluid
Nutrients
claudins
occludin
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
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