The Fort Worth Press - Protagonist Therapeutics Announces U.S. FDA Approval of Hepcidin Mimetic Peptide MIMRYLO(TM) (rusfertide) for Polycythemia Vera

NEWARK, CA / ACCESS Newswire / August 28, 2026 / Protagonist Therapeutics, Inc. (NASDAQ:PTGX) ("Protagonist" or "the Company") announced today that Takeda received U.S. Food and Drug Administration (FDA) approval for MIMRYLO (rusfertide), a subcutaneously delivered first-in-class hepcidin mimetic peptide for the treatment of erythrocytosis in adults with polycythemia vera (PV). MIMRYLO is the first and only hepcidin mimetic approved for polycythemia vera (PV), a blood cancer characterized by excessive production of red blood cells.

"Today's FDA approval of MIMRYLO represents a paradigm shifting approach to management of PV. MIMRYLO mimics the action of hepcidin, the body's natural master regulator of iron availability thereby controlling hematocrit levels and helping restore iron balance. MIMRYLO was conceived fourteen years ago with the idea that a mimetic of hepcidin, the body's primary regulator of iron homeostasis, could address the underlying biology of erythrocytosis in PV. The approved label also reflects improvement in fatigue as measured by PROMIS Fatigue Short Form 8a." said Dinesh V. Patel, PhD, President and Chief Executive Officer of Protagonist Therapeutics. "I am very proud of what the team at Protagonist, in partnership with investigators and patients, have accomplished in bringing this drug over the finish line, and we have full confidence in Takeda as the ideal partner to bring MIMRYLO to patients who need it most."

"This is Protagonist's second FDA approval in 2026, reflecting years of disciplined investment in the right type of innovative projects, and working with the right partners at the right time," Patel continued. "With two approved products validating our peptide-centric drug discovery and development acumen and a strong financial foundation, the Company is now focused on leveraging its expertise to advance the next generation of wholly owned product candidates in IL-17, obesity, and beyond with the intent of addressing unmet needs of patients and creating long-term value for our shareholders."

MIMRYLO will be commercialized by Takeda under the worldwide license and collaboration agreement entered into in 2024 between Protagonist and Takeda. Protagonist discovered rusfertide (PTG-300) and had primary responsibility for its development through Phase 3, with Takeda assuming responsibility for NDA submission and commercialization following Protagonist's opt-out election in April 2026.

FDA approval of MIMRYLO triggers $275 million in payments to Protagonist, consisting of a $200 million opt-out fee and a separate $75 million approval milestone. Protagonist is eligible to receive up to an additional $875 million in total potential milestone payments, as well as tiered royalties ranging from 14% to 29% on worldwide net sales, corresponding to approximately 21% on a weighted-average basis at $1.5 billion in annual sales.

Clinical evidence summary

MIMRYLO was approved on the basis of the Phase 3 VERIFY study, a randomized, double-blind, placebo-controlled trial in patients with polycythemia vera. In VERIFY, patients in the MIMRYLO arm achieved statistically significant benefit over the placebo arm, including the proportion of responders (with absence of phlebotomy eligibility), mean number of phlebotomies, proportion of participants maintaining hematocrit 15%) adverse reactions were injection site reactions (56%) and anemia (16%).

Conference Call and Webcast Details
The dial-in numbers for Protagonist's investor update on August 31^st at 8:30 am ET are:

US-based Investors: 1-877-407-0752
International Investors: 1-201-389-0912
Conference Call ID: 13762375

The webcast link for the event can be found here:

https://viavid.webcasts.com/starthere.jsp?ei=1773338&tp_key=7082945e97

A replay will be available on the Company's Investor Relations Events and Presentations webpage following the event.

Unmet Need in PV

PV is characterized by the excessive production of red blood cells (erythrocytosis), leading to elevated hematocrit which can increase blood viscosity, or thickness. This has the potential to result in life-threatening thrombotic events, including stroke, deep vein thrombosis and pulmonary embolism. Patients with PV may also experience burdensome symptoms, including severe fatigue, pruritus (itching), difficulty concentrating and night sweats. Patients with PV experiencing uncontrolled hematocrit have a four times higher risk of cardiovascular death or major cardiovascular events compared to patients who achieve a hematocrit of less than 45%¹. An estimated 78% of patients still experience uncontrolled hematocrit with current standard of care, including phlebotomy and cytoreductive therapies.

MIMRYLO^™ is a First-In-Class Treatment Option for Patients with PV

MIMRYLO is the first and only hepcidin mimetic peptide approved for the treatment of erythrocytosis in adults with polycythemia vera (PV). Rusfertide mimics the action of the natural hormone hepcidin, the body's natural master regulator of iron availability, suppressing red blood cell production by reducing iron availability to erythroid progenitor cells, thereby controlling hematocrit levels. Unlike current standards of care, which include phlebotomy and cytoreductive therapy and do not address the mechanism of iron dysregulation in PV, MIMRYLO directly targets red blood cell overproduction in PV. In the Phase 3 VERIFY study, 76.9% of patients receiving MIMRYLO plus current standard of care achieved a clinical response during Weeks 20-32, compared with 32.9% of patients receiving placebo plus current standard of care. The study also demonstrated improvement in fatigue as measured by PROMIS Fatigue Short Form 8a. For patients who have spent years managing a chronic, burdensome disease through frequent blood draws and ongoing cytoreductive therapy, MIMRYLO represents a fundamentally different approach, leveraging the body's natural regulatory systems to control hematocrit and help restore iron balance. MIMRYLO is self-administered as a weekly subcutaneous injection. MIMRYLO is currently approved in the U.S. for the treatment of erythrocytosis in adults with PV. Full prescribing information is available on the MIMRYLO website.

MIMRYLO^™ IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

• New or Worsening Thrombocytosis: MIMRYLO may increase platelet counts in patients with PV. Platelet counts generally plateaued on treatment by Week 8. After initiating MIMRYLO and during dose modifications, monitor CBC every 2 to 4 weeks or as clinically indicated. Platelet elevations associated with MIMRYLO may require cytoreductive therapy initiation, modification, or MIMRYLO dose modifications or discontinuation.

• Injection-Site Reactions: Injection site reactions (including Grade 3 reactions) have been reported in patients treated with MIMRYLO. The most common injection site reactions reported were erythema, pruritus, pain, and swelling. Use ice, topical corticosteroid creams, antihistamines or analgesics, as needed, to treat injection site pain and swelling.

• Embryo-Fetal Toxicity: Based on findings from animal reproduction studies, MIMRYLO may cause fetal harm when administered to a pregnant woman. Advise patients to stop taking MIMRYLO if they become pregnant.

ADVERSE REACTIONS

The most common (>15%) adverse reactions were injection site reactions (56%) and anemia (16%).

USE IN SPECIFIC POPULATIONS

• Lactation: Because of the potential for serious adverse reactions in the breastfed child, including impaired iron absorption, advise patients not to breastfeed during treatment with MIMRYLO and for 30 days after the final treatment.

• Females and Males of Reproductive Potential

  • Pregnancy Testing: Prior to initiating MIMRYLO, pregnancy testing is recommended for females of reproductive potential.

  • Contraception: Advise female patients of reproductive potential to use effective contraception during treatment with MIMRYLO and for at least 30 days after the final dose of MIMRYLO.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-844-662-8532 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see MIMRYLO (rusfertide) full Prescribing Information.

About Protagonist

Protagonist Therapeutics is a biopharmaceutical company built on a proprietary peptide technology platform that has now produced two FDA-approved, first-in-class medicines, generating royalties and milestones from global commercial partnerships with Johnson and Johnson and Takeda Pharmaceutical Company Limited. ICOTYDE^™ (icotrokinra), licensed to Johnson & Johnson company Janssen Biotech, Inc., is the first and only targeted oral peptide that precisely blocks the Interleukin-23 receptor. ICOTYDE was launched in the U.S. in March 2026 for the treatment of moderate-to-severe plaque psoriasis in adults and pediatric patients 12 years of age or older and is in Phase 3 development for psoriatic arthritis, ulcerative colitis and Crohn's disease. ICOTYDE was jointly discovered by Protagonist and Johnson & Johnson scientists, with Protagonist having primary responsibility for the development of ICOTYDE through Phase 1, and Johnson & Johnson assuming responsibility for further clinical and regulatory development and commercialization. Protagonist also discovered and led research and development through Phase 3 for MIMRYLO^™ (rusfertide), a first-in-class hepcidin mimetic peptide licensed to Takeda Pharmaceutical Company Limited for worldwide commercialization. MIMRYLO is approved in the U.S. for the treatment of erythrocytosis in adults with PV. The Company also has a number of clinical and preclinical programs based on clinically and commercially validated targets and addressing unmet medical needs, including an oral IL-17 antagonist peptide, anti-obesity dual and triple agonists, an oral hepcidin functional mimetic, and the recently announced IL-4 and amylin discovery programs.

More information on Protagonist, its pipeline drug candidates, and clinical studies can be found on the Company's website at https://www.protagonist-inc.com.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the potential benefits of MIMRYLO and potential revenue from the Company's collaboration with Takeda. In some cases, you can identify these statements by forward-looking words such as "anticipate," "believe," "may," "will," "expect," or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, our ability to earn milestone payments under our collaboration agreements with Janssen and Takeda, our ability to use and expand our programs to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, and our ability to obtain and adequately protect intellectual property rights for our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the Securities and Exchange Commission, including under the heading "Risk Factors" contained in our most recently filed periodic reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition, and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements, whether as a result of new information, future events, or otherwise, after the date of this press release.

Investor Relations Contact

Corey Davis, Ph.D.
LifeSci Advisors
[email protected]
+1 212 915 2577

Media Relations Contact

Virginia Amann
ENTENTE Network of Companies
[email protected]
+1 833 500 0061 ext 1

View the original press release on ACCESS Newswire

A.Maldonado--TFWP