Tissue Dynamics Ltd. and Galmed Pharmaceuticals Ltd. (NASDAQ:GLMD) ("Galmed" or the "Company"), a clinical-stage biopharmaceutical company focused on liver, cardiometabolic, and GI oncology diseases, today announced results from a preclinical study evaluating a combination of Aramchol Meglumine, an SCD1 inhibitor, and a selective PPARα agonist. The study identified a previously unrecognized metabolic pathway involved in the progression of cardiac fibrosis and heart failure and demonstrated that the two-drug combination effectively targets this mechanism.

 

Progressive cardiac fibrosis, driven by ischemic injury or age-related metabolic dysfunction, results in pathological scarring of the heart muscle, leading to tissue stiffening and impaired systolic and diastolic function. Cardiac fibrosis is a major contributor to heart failure progression and remains an area of significant unmet medical need. Despite advances in cardiovascular care, no therapies directly reverse established cardiac fibrosis, highlighting the need for novel therapeutic approaches.

One of the major challenges in cardiac drug development is the substantial physiological and metabolic differences between rodent and human hearts. As a result, findings from animal models often fail to translate successfully into human clinical outcomes. Using its robotic DynamiX® platform and advanced human cardiac organoid models, Tissue Dynamics identified a novel human-specific metabolic mechanism that would not have been readily detectable using conventional animal models.

The study demonstrated that a combination of Aramchol Meglumine and a selective PPARα agonist modulates two key pathological processes—mitochondrial stress and associated lipogenesis—that contribute to the development and progression of cardiac fibrosis and heart failure. Leveraging Tissue Dynamics' machine-learning platform, researchers identified and validated a previously unknown metabolic pathway underlying the synergistic effects of the combination therapy. In inflammatory human cardiac organoids, the treatment reduced fibrotic burden by approximately fourfold (p<0.001) while preserving cardiac muscle density and maintaining metabolic function. Based on these findings, a new patent application has been filed, and preparations are underway to support future IND-enabling activities.