Jul. 19 at 9:51 PM
$AGMB The other interesting aspect of Agomab’s molecule is that it shouldn’t reach creeping fat, meaning this MoA relies on the cross-talk between the intestine to the CR to downregulate pro-fibrotic factors. However, it IS thought to affect the interface between the gut wall and the fat, e.g. the specific repository of CTHRC1+ fibroblasts that may be particularly pathogenic.
The key to controlling fibrosis seems to be targeting something that has broad downstream effects. When you look at successful treatments of fibrosis in other conditions such as IPF you’ve got one that targets three different receptors (nintedanib), one that targets cAMP (nerandomilast), blocking both inflammation and fibrosis, and one that targets both the TNF and TGFB pathways (pirfenidone). Interestingly,
$PALI is using a gut-restricted version of the same MoA as nerandomilast (PDE4) to treat IBD as well. But the TGF-B pathway would be the golden goose for eliminating fibrosis IF you can do it safely.
