Matriptase-2 Pathway Inhibitor

Disc Medicine is developing a first-in-class, oral inhibitor of matriptase-2 (Mat-2) 
to induce endogenous expression of hepcidin. By increasing hepcidin levels to reduce iron levels, 
our program has the potential to address a wide range of hematologic diseases.

Biological Role of Matriptase-2

Matriptase-2 (Mat-2) plays a critical and specific function in iron metabolism by limiting the production of hepcidin. Mat-2 is a serine protease encoded by the gene TMPRSS6 and selectively degrades hemojuvelin, a receptor required for hepcidin expression. By inhibiting matriptase-2, our program is designed to increase the production of hepcidin to therapeutically reduce iron. This mechanism has been validated by human genetics, where patients with mutations in TMPRSS6 develop elevated hepcidin levels and an iron restrictive phenotype.

Potential Applications

There is a growing body of clinical and preclinical evidence that therapeutic hepcidin plays an important role in a wide range of hematologic diseases. This includes conditions such as polycythemia vera (PV), hereditary hemochromatosis, myelodysplastic syndromes (MDS) and β-thalassemia. Across these disease states, patients develop dangerously high levels of iron, resulting in complications that impact survival and daily life. While a number of injectable options are currently in development to increase or mimic hepcidin function, we believe there is a significant need for an effective oral treatment to provide optimal control of iron levels, as these conditions require chronic therapy.

Development Stage

Our matriptase-2 inhibitor program is currently in preclinical development. We have identified numerous, specific inhibitors and demonstrated their effects on hepcidin and iron metabolism in animal studies and plan to advance a lead candidate into clinical studies.