By exercising its opt-out right during the contractual opt-out period, Protagonist becomes eligible to receive up to $400 million in opt-out payments, consisting of $200 million payable upon the opt-out election and a further $200 million payable upon FDA approval of rusfertide for the treatment of adults with PV. In addition, U.S. approval of rusfertide would trigger a $75 million milestone payment, bringing total potential cash payable in connection with the opt-out election and U.S. approval to $475 million.

As a result of the opt-out election, Takeda now holds exclusive development and commercialization rights to rusfertide in the United States, in addition to its existing exclusive ex-U.S. rights. Under the opt-out structure, Protagonist becomes eligible to receive up to $975 million in milestone payments and tiered royalties on worldwide net sales ranging from 14% to 29%, corresponding to a weighted-average royalty rate of approximately 21% at $1.5 billion in annual net sales, with the top royalty tier of 29% applying to annual net sales above $1.5 billion.