May 16, 2022 The 2nd A-TANGO General Assembly was held on 11–13 May 2022 in Castelldefels, Spain More than one year after the kick-off meeting meeting of the EU-funded A-TANGO project, participants at partner institutions met for three days in Castelldefels, Spain, to discuss progress and the challenges of conducting a clinical trial to test the effectiveness and safety of a novel combinatorial therapy for the treatment of acute-on-chronic liver failure (ACLF)

BARCELONA—The A-TANGO General Assembly meeting brought together early career researchers, industry experts and leading clinical researchers participating in this project to review progress and celebrate the achievements accomplished to date.

On day 1, early career-researchers had the opportunity to learn about medical device design and entrepreneurship from Daniel Green, CEO at Yaqrit Ltd., UK. The General Assembly officially started with a lecture by Thomas Berg, Head of Division at Leipzig University Medical Center, Germany, and Vice Secretary General of the European Association for the Study of the Liver (EASL). Berg shared his insights on most recent advances in the treatment of cirrhosis and ACLF.

Coordinator of A-TANGO Rajiv Jalan, Professor of Hepatology at University College London, UK, and Scientific Director at the European Foundation for the Study of Chronic Liver Failure (EF CLIF), Spain, welcomed all participants at the opening of the General Assembly meeting on day 2. Cornelius Engelmann, clinical researcher and consultant at Charité–Universitätmedizin Berlin, Germany, and clinical trail coordinator for the A-TANGO project, discussed the current understanding of liver regeneration in ACLF and the relevance of recent findings from his group. Ed Guillabert, Head of Chemistry, Manufacturing and Controls at Hepyx Ltd., UK, presented the plan for drug manufacturing, packaging and distribution. Noelia Rodriguez, Finance Director at Alpha Bioresearch SL, Spain, provided an update on the ethical review process to run the clinical trial and confirmed submission of the study protocol, investigator brochure, patient information sheet, informed consent form and insurance certificate to regulatory authorities in the UK. Engelmann presented the study design to conduct a randomized, placebo-controlled clinical trial using G-TAK (G-CSF + TAK-242) in steroid-resistant alcoholic hepatitis and ACLF patients. Next, a round table moderated by Jalan discussed relevant aspects related to regulatory and ethical issues, clinical trial design, industry participation and conflict of interest. At the afternoon session, Fausto Andreola, Senior Research Fellow at University College London, UK, presented an update on the preparation of standard operational protocols for the collection and handling of patient samples. Carlos de la Peña, Statistician at EF CLIF, presented an update of the data management plan. Dirk Hasenclever, Professor at University of Liepzig, Germany, who serves as Data and Safety Monitoring Committee member, provided an overview of the statistical issues associated with early phase clinical trials and put these theoretical principles into perspective with the A-TANGO objectives.

Michal Kowalski, Technical Director at Hepyx Ltd., discussed about treatment cost estimations of G-TAK treatment and the challenges of engaging with investors. Karen Church, Head of Regulatory Affairs and Quality Assurance at Yaqrit Ltd., explained the strategy behind orphan drug designation in the US vs. Europe. Louise Perrault, President and CEO of International Market Access Consulting GmbH, Switzerland, discussed about reimbursement. Isabel Durand-Zaleski, Chief of Health Economics and Health Services Research at Assistance Publique Hôpitaux de Paris, France, provided her insights on economic evaluation (i.e., the assessment of the efficiency and allocation of resources to G-TAK treatment and the health outcomes compared to standard of care. Next, Magdalena Tyndyk, Project Manager at Crowdhelix, Ireland, provided an overview of the Liver Health Helix within the Crowdhelix platform as a tool to connect with the scientific community, industry and potential investors. At the end of the day, Céline Gravot, Project Manager at Concentris GmbH, Germany, provided an overview of the status of the overall project in terms of deliverables and milestones.

On day 3, participants in the mentor-mentee program met before the morning session started to review major progress of early career researchers towards their learning and professional goals. Nina Donner, Project Manager at Concentris, reviewed former communication and dissemination activities and presented the plan for the next 6 months. Ways to increase the visibility of the project at most prestigious international conferences were discussed and key messages addressed to different audiences defined. Next Veronika Vsetickova, Office Manager at the European Liver Patients' Association (ELPA), provided an overview of the role of the Impact Board in overseeing all dissemination and communications, and exploitation activities. At last, Prof. Dr. Emeritus Geoffrey Dusheiko and Prof. Dr. Emeritus Tilman Sauerbruch, both members of the Scientific and Ethical Advisory Board together with Hasenclever on behalf of the Data and Safety Monitoring Committee shared valuable advice to overcome current and future challenges. They all highlighted the many strengths of the proposal and recognized the expertise of partners and the importance of conducting this clinical trial to further knowledge to improve treatment for patients with cirrhosis and ACLF.

This study received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 945096.

About A-TANGO

The EU-funded A-TANGO project aims to bring a novel treatment (G-TAK) that combines a drug known to targets inflammation (TAK-242) and granulocyte colony-stimulating factor (G-CSF) which improves hepatocyte proliferation. Alongside the identification of novel biomarkers for patient selection and prognosis, G-TAK is expected to improve the clinical outcome of patients with alcoholic liver disease who are at high risk to develop acute-on-chronic liver failure (ACLF). The A-TANGO Consortium will perform a phase IIb randomized controlled trial to evaluate the safety and effectiveness of this novel treatment.

About EF Clif

The European Foundation for the Study of Chronic Liver Failure (EF Clif) is a private nonprofit organization which mission is to promote research and education in hepatic chronic failure with the aim to contribute to improving the quality of life and to increase the survival of patients with liver cirrhosis. Since its foundation in 2009, the European Association for the Study of the Liver (EASL) Chair supports research activities through the EASL-Clif Consortium, a network of more than 100 European university hospitals and more than 170 clinical researchers. The Grifols Chair promotes translational studies across centers throughout Europe and North America within the framework of the European Network for Translational Research (ENTR) with 25 centers and more than 40 investigators.