DELIVER
Laureate of the prestigious ANR call “Recherche Hospitalo-Universitaire en santé (RHU)”, DELIVER is a cutting-edge public-private R&D program that will combine patient-derived models, and integrate the latest imaging technologies with AI and large prospective cohorts of patients included in hepatocellular carcinoma (HCC) surveillance programs, to deliver therapeutic innovation for advanced liver fibrosis and HCC.
Advanced liver fibrosis and cancer, such as HCC, are particularly difficult to treat. For liver fibrosis there are no approved therapies. HCC is a leading cause of cancer-related death, with close to a million deaths worldwide in the year 2020. What is more alarming is the increasing incidence of advanced liver fibrosis and HCC due to fatty liver disease, which is mainly related to poor diet, sedentary lifestyle, and a growing aging population.
Collectively, DELIVER provides a cutting-edge program to transform the care of patients affected by advanced liver disease and cancer by delivering innovative solutions on multiple fronts. This multidisciplinary project integrates: the clinical evaluation of an innovative biotherapy discovered by Prof. Baumert’s team and developed by Alentis, the development of novel models to discover candidate combination therapies, and the characterization of circulating and imaging biomarkers to enable precision medicine of advanced liver diseases and cancer.
Project information
Start date: 01/07/2022 – End date: 30/06/2027 – Budget: €6.7 m
Consortium
DELIVER brings together a strong multidisciplinary international consortium which combines research and clinical excellence at the Institute of Translational Medicine and Liver Disease (ITM), IHU Strasbourg, and University Sorbonne Paris Nord – AP-HP in Paris, drug development know-how and agility in the biotechnology company Alentis, together with medical imaging innovation brought by the Guerbet Group.
Our complementary expertise and knowledge will ensure fast-track clinical development and translation to the patient.
Progress to date
The DELIVER project started in 2022. The scientific program is ongoing as planned and all milestones have been met and deliverables completed on time. Alentis is fulfilling the clinical development of Claudin-1 specific monoclonal antibody ALE-F02 with a first-in-human clinical trial. Following a Phase 1 completed in healthy volunteers, a Phase 1b FEGATO-01 study investigating safety, pharmacokinetics and target engagement in patients with advanced liver fibrosis was conducted and successfully completed.
Concerted work from Guerbet, AP-HP, Inserm and IHU Strasbourg is currently ongoing to discover new imaging and blood biomarkers. The completion of fully annotated CT, MRI and US prospective databases have been achieved. The development of deep learning models to exploit these data for early-stage detection of HCC has been initiated, with very promising early results. Moreover, we identified a panel of blood biomarkers potentially predictive for HCC risk in diseased patients.
In Inserm U1110, the development of a next generation patient-derived models is ongoing, with one humanized Claudin-1 mouse model successfully established and the completion of a liver-on-a-chip prototype. Finally, the study of Claudin-1 in liver cancer biology has unraveled a previously unknown role of Claudin-1 in pro-oncogenic signaling and reprogramming of the tumor microenvironment. Preclinical proof-of-concept studies to treat liver cancer with anti-Claudin-1 monoclonal antibodies have been successfully completed.
Publications
Crouchet E, Almeida N, Durand SC, et al. A patient-derived HCC spheroid system to model the tumor microenvironment and treatment response. JHEP Rep. 2025, 7, 1–14. doi: 10.1016/j.jhepr.2024.101252.
Crouchet E, Dachraoui M, Jühling F, et al. Targeting the liver clock improves fibrosis by restoring TGF-β signaling. J Hepatol. 2025;82(1):120-133. doi: 10.1016/j.jhep.2024.07.034.
Nahon P, Lusivika-Nzinga C, Merle P, et al. Value of non-invasive test dynamics in guiding HCC surveillance decisions after HCV cure in patients with cirrhosis, J Hepatol, 2025. doi: 10.1016/j.jhep.2025.02.008.
Dana J, Meyer A, Paisant A, et al. Improving risk stratification and detection of early HCC using ultrasound-based deep learning models. JHEP Rep. 2025;7(10):101510. Published 2025 Jul 5. doi:10.1016/j.jhepr.2025.101510
Del Zompo F, Crouchet E, Ostyn T, et al. Claudin-1 is a mediator and therapeutic target in primary sclerosing cholangitis. J Hepatol. 2025;83(6):1305-1319. doi:10.1016/j.jhep.2025.08.005
Nahon P, Lusivika-Nzinga C, Merle P, et al. Value of non-invasive test dynamics in guiding HCC surveillance decisions after HCV cure in patients with cirrhosis. J Hepatol. 2025;83(3):701-711. doi:10.1016/j.jhep.2025.02.008
Roca Suarez AA, Jühling F, Moehlin J, et al. Protein tyrosine phosphatase delta is a STAT3-phosphatase and suppressor of metabolic liver disease. eGastroenterology. 2025;3(1):e100159. Published 2025 Jan 27. doi:10.1136/egastro-2024-100159
Galvanin C, Buch S, Nahon P, Trépo E. PNPLA3 in Alcohol-Related Liver Disease. Liver Int. 2025;45(1):e16211. doi:10.1111/liv.16211
Ganne-Carrié N, Nahon P. Differences between hepatocellular carcinoma caused by alcohol and other aetiologies. J Hepatol. 2025;82(5):909-917. doi:10.1016/j.jhep.2024.12.030
Nahon P. Establishing five-year overall survival as a new standard for trials in advanced HCC. J Hepatol. 2025;83(4):833-834. doi:10.1016/j.jhep.2025.05.001
Desert R, Gianonne F, Saviano A, et al. Improving immunotherapy for the treatment of hepatocellular carcinoma: learning from patients and preclinical models. Gut Liver. 2025;2(1):s44355-025-00018-y. doi:10.1038/s44355-025-00018-y
Nahon P, Ronot M, Sutter O, et al. Study protocol for FASTRAK: a randomised controlled trial evaluating the cost impact and effectiveness of FAST-MRI for HCC suRveillance in pAtients with high risK of liver cancer. BMJ Open. 2024 Feb 17;14(2):e083701. doi: 10.1136/bmjopen-2023-083701.
Nahon P, et al. The clinical and financial burden of nonhepatocellular carcinoma focal lesions detected during surveillance of patients with cirrhosis. Hepatology 79(4):p 813-828, April 2024. doi: hep.0000000000000615
Dana J, Sutter O. Prognostic stratification in early-stage hepatocellular carcinoma: imaging biomarkers are needed. Liver Int. 2024;44(4):881-883. doi: 10.1111/liv.15869.
Meyer A, Mazellier JP, Dana J, Padoy N. On-the-Fly Point Annotation for Fast Medical Video Labeling. Int J CARS 19, 1093–1101 (2024). doi: 10.1007/s11548-024-03098-y.
Crouchet E, Baumert TF. Unraveling the role of the liver myeloid compartment during hepatitis C virus cure. J Hepatol. 2024;80(2):184-187. doi: 10.1016/j.jhep.2023.04.016.
Saviano A, Roehlen N, Baumert TF. Tight Junction Proteins as Therapeutic Targets to Treat Liver Fibrosis and Hepatocellular Carcinoma. Semin Liver Dis. 2024; 44(02): 180-190. doi: 10.1055/s-0044-1785646.
Mukherji A., et al. An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection. Nat Commun 15, 7486 (2024). doi: 10.1038/s41467-024-51698-8.
Crouchet E, Dachraoui M, Jühling F, et al. Targeting the liver clock improves fibrosis by restoring TGF-β signaling. J Hepatol. 2025;82(1):120-133. doi:10.1016/j.jhep.2024.07.034
Dana J, Sutter O. Prognostic stratification in early-stage hepatocellular carcinoma: Imaging biomarkers are needed. Liver Int. 2024;44(4):881-883. doi: 10.1111/liv.15869.
Yang, S., Bône, A., Decaens, T., Glaunes, J.A. Refining Deep Learning Segmentation Maps with a Local Thresholding Approach: Application to Liver Surface Nodularity Quantification in CT. In: Ali, S., van der Sommen, F., Papież, B.W., Ghatwary, N., Jin, Y., Kolenbrander, I. (eds) Cancer Prevention, Detection, and Intervention. CaPTion 2024. Lecture Notes in Computer Science, vol 15199. Springer, Cham. doi: 10.1007/978-3-031-73376-5_10.
Crouchet E, Baumert TF. Unraveling the role of the liver myeloid compartment during hepatitis C virus cure. J Hepatol. 2024;80(2):184-187. doi: 10.1016/j.jhep.2023.04.016.
Nehme Z, Roehlen N, Dhawan P, Baumert TF. Tight Junction Protein Signaling and Cancer Biology. Cells 2023, 12, 243. doi: 10.3390/cells12020243
Roehlen N, et al. Treatment of HCC with claudin-1-specific antibodies suppresses carcinogenic signaling and reprograms the tumor microenvironment. J Hepatol. 2023 Feb;78(2):343-355. doi: 10.1016/j.jhep.2022.10.011
Désert R, Giannone F, Schuster C, Baumert TF. Tumor microenvironment-derived serum markers as a new frontier of diagnostic and prognostic assessment in biliary tract cancers. Int J Cancer. 2023 Mar 1;152(5):804-806. doi: 10.1002/ijc.34357
Nahon P, et al. Integrating genetic variants into clinical models for hepatocellular carcinoma risk stratification in cirrhosis. J Hepatol. 2023 Mar;78(3):584-595. doi: 10.1016/j.jhep.2022.11.003
Moreau C, et al. Dynamic personalized prediction of the individual liver-related risk after sustained viral response in HCV patients. J Viral Hepat. 2023 Jun;30(6):567-577. doi: 10.1111/jvh.13830
Cannella R, et al. Adherence to LI-RADS and EASL high-risk population criteria: A systematic review. Hepatology. 2023 Jun 1;77(6):1958-1967. doi: 10.1097/hep.0000000000000321
Ronot M, Nahon P, Rimola J. Screening of liver cancer with abbreviated MRI. Hepatology 78(2):p 670-686. doi: hep.0000000000000339
Singal AG, et al. International Liver Cancer Association (ILCA) white paper on hepatocellular carcinoma risk stratification and surveillance. J Hepatol. 2023 Jul;79(1):226-239. doi: 10.1016/j.jhep.2023.02.022
Mulé S, Ronot M, et al. Automated CT LI-RADS v2018 scoring of liver observations using machine learning: A multivendor, multicentre retrospective study. JHEP Rep. 2023 Jul 22;5(10):100857. doi: 10.1016/j.jhepr.2023.100857
Innes H, Nahon P. Statistical perspectives on using hepatocellular carcinoma risk models to inform surveillance decisions, J. Hepatol., 2023, 79, 1332–1337. doi: 10.1016/j.jhep.2023.05.005
Roehlen N, et al. A monoclonal antibody targeting non-junctional claudin-1 inhibits fibrosis in patient-derived models by modulating cell plasticity. Sci Transl Med. 2022 Dec 21;14(676):eabj4221. doi: 10.1126/scitranslmed.abj4221