Takeda's $300 Million Prepayment: Introduction of Protagonist's Hepcidin Analog, a Drug Developed Exclusively by Maiwei Biotech in China

In a significant move, Takeda Pharmaceuticals has announced a $300 million prepayment for the introduction of Protagonist Therapeutics' investigational drug Rusfertide, an analog of Hepcidin. This groundbreaking drug has been exclusively developed by Maiwei Biotech, making it the only company in China conducting research on similar medications. The partnership between Takeda and Protagonist Therapeutics grants Takeda 50% of the commercial rights in the United States, as well as rights outside the country.

Details of the Prepayment and Collaboration:

As part of the agreement, Takeda will make a hefty $300 million prepayment to Protagonist Therapeutics. Additionally, there will be milestone payments and sales royalties for markets outside the United States. Rusfertide, a hepcidin mimetic, is currently in Phase III clinical trials for the treatment of hereditary hemochromatosis, a condition characterized by excessive iron absorption in the body. It is expected that patient enrollment will be completed in the first quarter of 2024.

Understanding Iron Metabolism and the Role of Hepcidin:

Iron is an essential mineral that the human body absorbs daily from food, typically around 1-2mg. Iron from food enters the bloodstream through intestinal epithelial cells via a protein called ferroportin (FPN). Once in the blood, iron binds with transferrin and is transported throughout the body. The primary site of iron utilization is in red blood cells, while excess iron is stored in organs such as the liver. Iron from aging or dying red blood cells is recycled by macrophages. The level of iron in the body is tightly regulated by a hormone called hepcidin, encoded by the HAMP gene. Hepcidin expression is influenced by iron and red blood cells, creating a sophisticated feedback control system.

Implications for Hereditary Hemochromatosis:

Hereditary hemochromatosis is characterized by excessive production of red blood cells, leading to a severe chronic disease with an increased risk of thrombosis and cardiovascular complications. In the United States alone, there are approximately 100,000 cases of hereditary hemochromatosis. Drug development targeting iron metabolism can focus on different aspects and involve various targets, with hepcidin playing a crucial role. By developing hepcidin analogs, such as Rusfertide, it is possible to amplify its function or target other proteins like TMPRSS6 and FPN to upregulate hepcidin levels.

Exclusive Research Efforts by Maiwei Biotech:

In China, Maiwei Biotech stands out as the only company conducting innovative research on the hepcidin pathway. Their subsidiary in the United States has independently developed a monoclonal antibody drug called 9MW3011, which targets TMPRSS6. This novel drug works by binding to TMPRSS6 on the surface of liver cells, increasing the expression of hepcidin and modulating iron absorption and release, thereby maintaining iron homeostasis in the body. The clinical trial application for 9MW3011 injection was approved by the FDA in November 2022, allowing for clinical trials in patients with hereditary hemochromatosis. In January 2023, the trial application also received approval from the National Medical Products Administration in China, enabling clinical trials for indications related to iron overload in patients with hereditary hemochromatosis and β-thalassemia. Currently, the drug is in Phase I clinical trials.

Partnership with DISCMEDICINE, INC.:

In January 2023, Maiwei Biotech entered into an exclusive licensing agreement with DISCMEDICINE, INC. Under this agreement, DISCMEDICINE gains exclusive rights to develop, produce, commercialize, and otherwise exploit 9MW3011 in all regions except Greater China and Southeast Asia. Maiwei Biotech stands to receive a total upfront and milestone payment of up to $412.5 million, in addition to royalties on net sales of the licensed product, reaching nearly double-digit percentages. As part of the agreement, DISCMEDICINE has already made a non-refundable upfront payment of $10 million to Maiwei Biotech.

The partnership between Takeda Pharmaceuticals and Protagonist Therapeutics marks a significant milestone in the development of Rusfertide, a hepcidin analog with the potential to revolutionize the treatment of hereditary hemochromatosis. With exclusive research efforts by Maiwei Biotech focusing on the hepcidin pathway, particularly with their innovative drug 9MW3011, there is renewed hope for patients suffering from iron metabolism disorders. This collaboration presents a promising avenue for advancing the field of iron metabolism therapeutics and addressing the unmet medical needs of patients worldwide.