Understanding the problem
There is a worldwide rise in cases of liver disease, but few options for treatment.
The Yaqrit approach is based on 20 years' work by Professor Rajiv Jalan of University College London and his team and collaborators. Our approach to treating patients with liver disease is based on the understanding that many liver diseases share a common pathology: gut bacteria change (gut dysbiosis) and the gut wall becomes damaged. This leads to bacterial product that would notmally be excreted crossing the gut wall (translocation) to the liver. There, they are dealt with by the immune system, and repair mechanisms address any damage to the liver. If that immune response lasts years or decades, then this continuous immune response can lead successively to scarring, loss of function and, eventually to liver failure. These translocated bacterial products are collectively called bacterial endotoxins or lipopolysaccharides (LPS). It is the goal of Yaqrit’s technologies to remove LPS from the gut and from the blood.
• More than 640,000 cirrhosis patients are admitted to hospitals in Europe every year*
• There are about 200,000 admissions with ACLF each year in Europe* and 90 day mortality is about 50%
• About 6000 liver transplantations take please every year in the US, and liver transplant costs can be over $1 million in the first 12 months**
* Market analysis based on hospitalization and data from the Canonic Study (1343 Pts in 21 EU countries)
** http://www.healthline.com/health/liver-transplant-survival#overview1 and Habka D, Mann D, Landes R, Soto-Gutierrez A (2015) Future Economics of Liver Transplantation: A 20-Year Cost Modeling Forecast and the Prospect of Bioengineering Autologous Liver Grafts. PLoS ONE 10(7): e0131764. doi:10.1371/journal.pone.0131764
Disease Progression and Mortality
Liver disease, whether from alcohol or fatty liver is progressive, but the resilience of the liver can mask damage and disease until late stages. Patient with stable (“compensated”) liver disease can enter an acute (“decompensated”) phase that takes them into intensive care and a high risk of short term mortality. It is among Yaqrit’s early goals to treat both advanced liver disease (“cirrhotics”) and patients whose liver decompensation has led to the failiure of one or more other organs (“Acute-on-Chronic Liver Failure” (ACLF)).
Patients can live with liver disease for years or even decades. The typical age of intensive care/emergency room admission of a patient with ACLF is in their 50s.
As well as liver failure, patients can be admitted and be at risk of early death with complications of liver disease such as hepatic encephalopathy (brain damage caused by liver disease).
The current standard of care is poorly-absorbed antibiotics - intended to kill gut bacteria - and laxatives. Yaqrit’s technologies target the products from these gut bacteria, the lipopolysaccharide (LPS) molecules. In healthy people, LPS is removed by natural processes. In chronic liver disease, these natural processes are inadequate because of an increase in gut bacterial (bacterial overgrowth), and damage to the gut wall. The consequent translocation of LPS across the gut wall leads to an immune response which can, over decades, lead to scarring, loss of function and eventually, to liver failure.
Prevention and Treatment of Cirrhosis and Non-Alcoholic Steato Hepatitis (NASH). Yaq-001 is a patented macroporous carbon delivered in sachets that binds to, and thereby removes, LPS from the gut. It is the macropores that are unique to Yaq-001 and which allow access for large molecules such as LPS to the vast internal surface area of carbon beads. By breaking the link between gut dysbiosis and liver disease, Carbalive works to reverse the decline in health of patients with liver disease.
Extra-corporeal liver support for Acute-on-Chronic Liver Failure (ACLF) - removes LPS from the blood and exchanges damaged albumin for fresh albumin. Older comparable technologies have worked on the principle that repairing albumin alone would be effective. But these technologies have not increased patient survival.
The above projects have received funding from the European Union's Horizon 2020 research and innovation programme under grant agreements No 634579 and 733057.
Any dissemination of results must indicate that it reflects only the author's view and that the Agency is not responsible for any use that may be made of the information it contains.
TLR4 antagonist (Yaq-005)
Toll-like receptor 4 recognises LPS and is up-regulated in patients with chronic liver disease. This makes chronic liver disease patients sensitive to the increases in LPS levels characteristic of both chronic and acute liver diseases, and in turn makes it a target for pharmaceutical intervention. The first application of this principle has been licensed to a third party