NOVEL TREATMENT OF ACUTE ON CHRONIC LIVER FAILURE USING SYNERGISTIC ACTION OF G-CSF AND TAK-242

In Europe, about 30,000 people die every year from alcohol related cirrhosis, a form of chronic, non- communicable disease.

The patients that are at highest risk of death are those with superimposed alcoholic hepatitis (AH) who do not respond to therapy and develop acute on chronic liver failure (ACLF), a newly described syndrome characterised by multiorgan failure. Treatment of ACLF is an unmet need.

Based upon their clinical and pre-clinical studies, the A-TANGO consortium aims to perform Phase 2 clinical trials of a novel, patented and innovative therapeutic strategy by repurposing a toll-like 4 receptor antagonist (TAK242, Technology Readiness Level (TRL) 8), which targets inflammation, and combining it with granulocyte colony-stimulating factor (G-CSF, TRL9) that improves hepatocyte proliferation (G-TAK, TRL4).

A successful trial will advance G-TAK to TRL8.

Additionally, A-TANGO aims to discover novel biomarkers for patient selection and defining prognosis, building health economics models and reimbursement strategies to allow maximal dissemination and exploitation.

The A-TANGO Consortium includes the inventors of G-TAK (UCL, Charit, ULEI and LUMC) and will deliver the project aims through EFCLIF, which has a network of 110 European hospitals. YAQ and HPX are SMEs that own the background IP and will ensure regulatory approval, study Sponsorship and drug supply.

APHP and IMAC will deliver the economic models.

Concentris will manage the project and together with EASL, CHX and ELPA will engage with patients, initiate widespread dissemination activities and allow exploitation of the results. Gender balance will be maintained throughout the project duration.

A-TANGO will achieve the expected impacts of producing meaningful advances in clinical practice by reducing the mortality and improving the quality of life of patients with ACLF whilst reducing disease burden of individual patients and health care systems following validation in late stage clinical trials.