Takeda and Protagonist Enter into Global License and Collaboration

Rare Daily Staff

Japanese pharmaceutical Takeda and Protagonist Therapeutics signed a worldwide license and collaboration agreement for the development and commercialization of Protagonist’s rare hematology asset rusfertide, currently in a pivotal phase 3 trial for the treatment of polycythemia vera.

Under the terms of the agreement, Protagonist will receive an upfront payment of $300 million and is eligible to receive additional worldwide development and regulatory milestone payments, as well as commercial milestones and tiered royalties on ex-U.S. net sales. Protagonist will remain responsible for research and development through the completion of the phase 3 clinical trial and U.S. regulatory approval. Takeda has rights for ex-U.S. development and is responsible for leading global commercialization activities.

Polycythemia vera (PV) is a rare chronic blood disorder characterized by excessive production of red blood cells. The hallmark manifestations of PV are increased red blood cell count and iron deficiency, putting patients at higher risk of cardiovascular and thrombotic events, such as heart attack and stroke, and often impacting quality-of-life with symptoms such as fatigue and confusion.

“This transformational deal allows Protagonist to focus on completion of phase 3, while leveraging Takeda’s global commercialization capabilities to immediately commence pre-commercial activities with a first-in-class new chemical entity,” said Dinesh Patel, president and CEO of Protagonist Therapeutics. “As we progress towards a fully integrated pharmaceutical company, this deal mitigates the inherent execution risks of a first-time commercial launch, optimizes the timing and enhances the scope for peak potential sales of rusfertide, while still allowing us to actively participate in the commercial experience and economics with a 50-50 profit split in the U.S. market.”

Rusfertide is an investigational injectable hepcidin mimetic peptide of the natural hormone hepcidin. Discovered through Protagonist’s peptide technology platform, rusfertide’s mechanism of action is thought to regulate iron homeostasis and control the absorption, storage and distribution of iron in the body. The randomized portion of the phase 2 REVIVE study of rusfertide in polycythemia vera achieved its primary endpoint. The long-term follow-up data from the 2-year open label extension were presented at the American Society of Hematology 2023 Annual Meeting in early December, which showed durable hematocrit control, decreased phlebotomy use, long-term tolerability and no new safety signals in patients with PV.

The deal builds upon Takeda’s experience in rare hematology and follows the recent U.S. Food and Drug Administration approval of Adzynma, Takeda’s treatment for congenital thrombotic thrombocytopenic purpura (cTTP), an ultra-rare blood clotting disorder.

Following U.S. regulatory filing, Takeda will lead commercialization of rusfertide with Protagonist holding an option to co-detail in the U.S. Under the terms of the agreement, Protagonist has the right to opt-out of the 50:50 profit share. In that event, Protagonist would be eligible to receive opt-out payments and enhanced milestone and royalty payments. Takeda would maintain full ex-U.S. rights under either scenario.

“The agreement with Protagonist represents an important step forward in our strategy of acquiring late-stage assets in the rare disease space to leverage our existing infrastructure and expertise,” said Julie Kim, president, U.S. Business Unit and U.S. country head, Takeda.

“It combines the strength of their science with the reach of our commercial organization, understanding of rare diseases, and most importantly, our focus on supporting patients through their journey.”

Photo: Dinesh Patel, president and CEO of Protagonist Therapeutics