Vascular Biogenics Ltd (VBLT)

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VB-703 seems to be the NASH jewel for VBLT.

http://link.springer.com/article/10.1007/s10620-016-4159-5

In the current report, we investigated the effect of VB-201 treatment on the development of NASH and liver fibrosis in a mouse model. In addition, we used VB-703, an unreported lecinoxoid designed in silico for improved efficacy, that does not affect monocytes migration, but exhibits increased inhibition of TLR-4 over VB-201. The results demonstrate that lecinoxoids restrict liver inflammation and profoundly ameliorate liver fibrosis.

The results demonstrate that VB-703 inhibits TLR-4-mediated signaling events and cytokine production with a profoundly higher degree of activity than VB-201 (Fig. 2a, b) but similar to VB-201’s inhibitory effect on TLR-2-mediated phosphorylation (Fig. 2c). Moreover, VB-703 showed annulled activity in the case of monocyte migration (Fig. 2d).

Analysis of inflammation mediators IL-1ß, IL-6, MCP-1, and IL-12/23p40 in the liver of NASH-induced mice showed that VB-703 for the most part significantly inhibited expression of pro-inflammatory mediators, whereas VB-201 significantly attenuated only the expression of IL-12/23p40 (Figs. 3a–d).

The results, presented in Fig. 4a, b, demonstrate that VB-703, more than VB-201 and even telmisartan, significantly restricted the development of liver fibrosis.

Functionally, VB-201 differs from VB-703 in its ability to also inhibit monocytes migration, but it is a weaker antagonist of TLR-4 than is VB-703. Nevertheless, our results demonstrate that significant effects of lecinoxoids on liver inflammation could be attained by targeting TLR-2 and predominantly TLR-4, since VB-703 was superior to VB-201 in inhibiting all of the inflammation mediators tested.

To conclude, small molecules oxidized phospholipids that strongly antagonize TLR-4 and inhibit monocytes migration should be further explored for their potential to treat subjects with NASH and liver fibrosis.