Protagonist Exercises Rusfertide U.S. Opt-Out Right Under Takeda Collaboration

Opt-out election makes Protagonist eligible for $200 million upon exercise and an additional $200 million upon FDA approval of rusfertide for polycythemia vera

Approval would also trigger a $75 million milestone payment, bringing total potential cash tied to the opt-out election and approval to $475 million

Protagonist becomes eligible for up to $975 million in milestone payments and tiered royalties ranging from 14% to 29% on worldwide net sales

NEWARK, CA / ACCESS Newswire / April 28, 2026 / Protagonist Therapeutics, Inc. (Nasdaq:PTGX) ("Protagonist" or the "Company") today announced that it has exercised its right to opt out of the 50:50 U.S. profit and loss sharing arrangement under its worldwide license and collaboration agreement with Takeda for rusfertide, an investigational first-in-class hepcidin mimetic peptide under U.S. Food and Drug Administration (FDA) Priority Review for the treatment of adults with polycythemia vera (PV).

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.

"Exercising our opt-out right reflects our conviction in rusfertide and secures what we believe is the most attractive risk-adjusted value outcome for Protagonist and its shareholders as the hepcidin mimetic peptide approaches a potential approval," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer of Protagonist Therapeutics. "This election provides meaningful near-term non-dilutive cash, materially enhances our long-term economic participation through milestones and worldwide royalties, and further strengthens our ability to invest in our broader pipeline and return value to shareholders. We value our partnership with Takeda and believe they are exceptionally well-positioned to maximize the global opportunity for rusfertide."

Rusfertide is under FDA Priority Review for the treatment of adults with PV, with a Prescription Drug User Fee Act (PDUFA) target action date in the third quarter of 2026. Under the parties' January 2024 collaboration agreement, Protagonist received a $300 million upfront payment and retained the right to elect either a 50:50 U.S. profit and loss share or an opt-out structure featuring enhanced payments, milestones, and worldwide royalties.

About RusfertideRusfertide is a first-in-class investigational subcutaneous treatment that mimics the action of hepcidin, a natural hormone that regulates iron homeostasis and red blood cell production. By targeting the underlying mechanism of iron dysregulation in polycythemia vera, rusfertide aims to reduce excess red blood cell production and help patients achieve sustained hematocrit control. The molecule demonstrated rapid, stable, and durable control of hematocrit in Phase 2 & 3 studies as part of the clinical development program for PV. Rusfertide was discovered and developed using Protagonist Therapeutics' proprietary peptide technology platform. Rusfertide was previously being co-developed in PV. 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. The program has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration, underscoring its potential to address significant unmet needs in a chronic hematologic disease with limited modern therapeutic innovation.

About Polycythemia Vera (PV)Polycythemia vera (PV) is characterized by the overproduction of red blood cells (erythrocytosis), which increases blood viscosity, or thickness, that can result in life-threatening thrombotic events such as stroke, deep vein thrombosis, and pulmonary embolism. Hematocrit (HCT) is the ratio of red blood cells to the total amount of blood in the body. Achieving and maintaining controlled HCT levels of