"LinXis’ linker-payload manufacturing technology published in Green Chemistry"

Read more

Products - Liver Disease

Chronic liver disease is a growing concern that affects millions.

Chronic liver disease is progressive - it goes through stages that are increasingly severe. Once the disease enters advanced stage, there is no medicine or drug that can relieve the condition. Advanced liver disease thus represents a hugely unmet medical need.

Hepatic Stellate Cells are Key to Fibrosis and Cirrhosis

Hepatic stellate cells are part of the healthy liver. When they become activated however, for example due to viral hepatitis, the stellate cells deposit fibrous tissue throughout the liver in a process known as fibrosis. The liver eventually becomes so riddled with fibrotic tissue that it is beyond repair. This end stage of liver disease, known as cirrhosis, often has fatal consequence.

In the healthy liver (left), hepatic stellate cells are quiescent. In liver disease (right), they become activated. Activated stellate cells produce fibrous matter and actively contract, scarring and crumpling up the liver.

Hepatic Stellate Cells are a Target for Selective Drug Delivery

Activated hepatic stellate cells can be calmed down by potent substances called kinase inhibitors. By themselves these inhibitors would never make good medicines because they act indiscriminately: While they would calm down activated hepatic stellate cells, they would also affect other cell types throughout the body. This would produce unacceptable side effects.

From the drug targeting perspective however, this situation represents a unique opportunity - because selective delivery of these kinase inhibitors to activated stellate cells would improve the disease without side effects.

The only requirement for this approach is the existence of target molecules that are exquisitely expressed by activated stellate cells, and not by other cells in the body. We have confirmed the existence of two of such markers.

Immune fluorescent confocal microscopy image of healthy liver (left) and cirrhotic liver (right). Disease-specific expression of IGF2R, one of the two potential target molecules expressed exquisitely by activated hepatic stellate cells, is evident (red signal).

Our Approach

At LinXis, we work at unlocking hepatic stellate cells as targets for selective drug delivery. We have generated patented carrier molecules that specifically bind to activated hepatic stellate cells. These carriers are based on single domain antibodies that are commonly known as nanobodies. Our solid experience in conjugation chemistry and our technology platform enable us to equip these carriers with potent kinase inhibitors, generating unique targeting constructs that are truly first-in-class.

Positive results from several preclinical studies have prompted us to gear up this R&D program, aiming at developing a lead product for clinical testing. In this innovative project, funded by several innovation grants, we closely collaborate with top-tier academic research groups.

LinXis approach of targeting activated stellate cells. Our patented conjugates are based on proprietary nanobody-like carrier molecules, which very selectively shuttle potent drugs, known as kinase inhibitors, to activated hepatic stellate cells only. Because drugs are delivered only where they are needed, our products are designed to be effective without major side effects.