Takeda and Protagonist Therapeutics, Inc. announced the signing of a worldwide license and collaboration agreement for the development and commercialization of rusfertide, an investigational injectable hepcidin mimetic peptide of the natural hormone hepcidin, currently in a pivotal Phase 3 trial, VERIFY, for the treatment of Polycythemia Vera (PV). 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. 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. This announcement builds upon Takeda's heritage in Rare Hematology and follows the recent U.S. Food and Drug Administration (FDA) 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.