DISC-3405

DISC-3405 (formerly MWTX-003) is a monoclonal antibody against
TMPRSS6 (Transmembrane Serine Protease 6, also known as Matriptase-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 TMPRSS6

Transmembrane Serine Protease 6 (TMPRSS6) plays a critical and specific function in iron metabolism by limiting the production of hepcidin. By inhibiting TMPRSS6, 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.

Development Status

DISC-3405 (formerly MWTX-003) was in-licensed from Mabwell Therapeutics. It received IND approval from the US FDA in November 2022 and was fast-tracked by the FDA in September 2023. We initiated a phase 1 clinical study in healthy volunteers in October 2023. Our plan is to develop DISC-3405 to treat multiple iron overload disorders, such a polycythemia vera, beta thalassemia, and other indications.