Periodic Reporting for period 1 - FibroTarg (Targeting kidney fibrosis by a novel myofibroblast specific small molecule inhibitor)
Reporting period: 2023-10-01 to 2025-03-31
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
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
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.
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.