Benevolent Platform Precision Medicine slide image

Benevolent Platform Precision Medicine

aSMA readout normalised to shSCR Target B - First in class programme targeting a previously undrugged target for the treatment of NASH • Structure enabled hit identification strategy commenced 3Q21 Al-enabled literature analysis was able to identify data showing target B is reported as being upregulated in NASH, with expression correlating to the degree of fibrosis in the liver • Mechanistically diverse from target A, building depth to our NASH portfolio 150 aSMA Collagen I readout normalised to shSCR 0 SCR shRNA + TGF-B1 hACTA2 shRNA Target shRNA #1 One way ANOVA with Dunnetts 100- 50- **** **** 2012 Target shRNA #2 Target shRNA #3 4 **** 150- 100- Collagen I 50- **** **** **** SCR shRNA + TGF-ẞ1 hTGFBR2 shRNA Target shRNA #1 Target shRNA #2 Target shRNA #3 **** Cell number normalised to shSCR 200- NS 150- 100- 50- I H * Cell count NS SCR shRNA + TGF-B1 hACTA2 shRNA hTGFBR2 shRNA * Target shRNA #1 Target shRNA #2 Target shRNA #3 SI NS TGF-activated immortalized human hepatic stellate cells ⚫ Fibrosis assay established in immortalised hepatic stellate cells • Lentiviral delivery of shRNA constructs to knock down target expression Three separate shRNA constructs were run independently for the target • Full target-story data package complete Al Benevolent 63
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