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 63View entire presentation