Targeting kidney fibrosis by a novel myofibroblast specific small molecule inhibitor

Información del proyecto

FibroTarg

Identificador del acuerdo de subvención: 101138549

DOI

10.3030/101138549

Proyecto cerrado

Fecha de la firma de la CE 4 Septiembre 2023

Fecha de inicio 1 Octubre 2023

Fecha de finalización 31 Marzo 2025

Financiado con arreglo a

• European Research Council (ERC)

Coste total

Sin datos

Aportación de la UE

€ 150 000,00

Coordinado por

UNIVERSITAETSKLINIKUM AACHEN
Germany

Periodic Reporting for period 1 - FibroTarg (Targeting kidney fibrosis by a novel myofibroblast specific small molecule inhibitor)

Período documentado: 2023-10-01 hasta 2025-03-31

Resumen del contexto y de los objetivos generales del proyecto

Chronic kidney disease (CKD) is a progressive disease representing a growing medical, societal and economic problem. The prevalence of CKD has now reached over 10% in the developed world. Furthermore, the global mortality rate from CKD across ages has increased by 41.5% over the past two decades, and CKD is predicted to become the 5th leading cause of death worldwide by 2040. Although in recent years sodium–glucose cotransporter 2 (SGLT2) inhibitors and novel mineralocorticoid antagonist are showing significant effect on CKD, the majority of patients treated still progress towards end-stage renal disease (ESRD). Fibrosis, i.e. tissue scar formation due to an excessive accumulation of extracellular matrix, is the common final pathway in virtually all chronic injury across organs and tissues. In CKD, fibrosis is responsible for slowly destroying the architecture of the kidney tissue. As a result, CKD patients gradually lose their kidney function and progress towards end-stage renal disease (ESRD) and kidney failure. Once CKD patients reach ESRD, the only available treatments are dialysis or kidney transplantation. While fibrosis has been recognized as a promising therapeutic target no specific anti-fibrotic therapy for the kidney exists.

In FibroTarg, we will assess the technical and commercial feasibility of a small myofibroblast specific inhibitor as a novel, first-of-its-kind anti-fibrotic drug candidate, for the treatment of chronic kidney disease (CKD). To reach proof-of concept, we envision the following activities:

1) Validation of the inhibitor as a drug candidate for CKD in in vitro models
2) Validation of the inhibitor as a drug candidate for CKD in in vivo models
3) Commercial feasibility assessment

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

We have tested a novel antifibrotic myofibroblast inhibitor fibrolisine in complex human 3D organoid assays and in mouse models of kidney fibrosis and have demonstrated efficacy with significant reduction of fibrosis. These data suggests that fibrolisine is a promising novel antifibrotic compound.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

We have performed an extensive market research for three fibrosis markets including kidney, heart and bone marrow indicating a massive market with over 4 Billion Euro. The next steps will be generation of IND-enabling data which will likely include several med-chem cycles and subsequent animal testing with large animal safety studies and tox studies.