MandalMed’s lead product is MM-003, a human protein that is an inhibitor of galectin-3, which is being developed to prevent and treat harmful remodeling after myocardial infarction (MI; heart attack) and, thereby, improve cardiac function and reduce mortality from subsequent heart failure. Secondly, MandalMed intends to develop MM-003 for chronic use in heart failure by performing biomarker-directed clinical studies. Elevated levels of galectin-3 in the serum have identified a subset of individuals with heart failure that have more progressive disease.
MI is the most common cause of heart failure and cardiac morbidity in the Western world. The incidence in the United States is approximately 610,000 new attacks and 325,000 recurrent attacks annually. Fibrosis is triggered by the physiological response to injury or infection and leads to the deposition of extracellular matrix proteins such as collagen and the formation of new connective tissue. Excessive or dysregulated fibrosis reduces the functioning of the heart by reducing contractility, elasticity, and distensibility, which exacerbate processes that lead to heart failure.
Although therapeutic agents currently used after MI such as the mineralocorticoid receptor antagonists (MRAs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) are efficacious and have shown anti-fibrotic effects in animal studies, the health burden from MI and subsequent heart failure remain very significant.
Galectin-3 is a key mediator of cardiac fibrosis and timely inhibition of galectin-3 after MI could improve the functionality of the heart and patient outcomes.
Section (left) of the entire myocardium of a rat at 28 days post-injury in an ischemia-reperfusion model with Masson’s trichrome staining (dark blue) for collagen deposition, which reveals the large primary lesion (black arrow). Section of a portion (right) of a rat myocardium at 28 days post-injury in an ischemia-reperfusion model with staining with Picro Sirius red to reveal collagen fiber accumulation (blue arrow) in the interstitial space between myocytes.