Takeda Pharmaceutical Co., Ltd.

− Study met the primary endpoint, with a significantly higher proportion of clinical responders on rusfertide compared to placebo − All four key secondary endpoints were met, including EU primary endpoint and patient-reported outcomes − Rusfertide was generally well tolerated; no new safety findings were observed in the study NEWARK, CA, USA & OSAKA, Japan & CAMBRIDGE, MA, USA I March 03, 2025 I Protagonist Therapeutics, Inc. (“Protagonist”) ( NASDAQ:PTGX ) and Takeda ( TSE:4502/NYSE:TAK ) today announced positive topline results for the Phase 3 VERIFY study, in which phlebotomy-dependent patients with polycythemia vera (PV) were randomized to treatment with either rusfertide or placebo, as an add-on to standard of care treatment. The study met its primary endpoint and all four key secondary endpoints. Rusfertide is a first-in-class investigational hepcidin mimetic peptide therapeutic, which has received Orphan Drug designation and Fast Track designation from the U.S. Food & Drug Administration (FDA). Key findings from the study include: “The positive results of the Phase 3 VERIFY study across the primary and all key secondary endpoints provide compelling evidence of the potential for rusfertide as a first-in-class erythrocytosis-specific agent to address unmet medical needs in patients with PV who are unable to achieve adequate hematocrit control despite standard of care treatments,” said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist. “We plan to submit additional details of these promising results for presentation at upcoming medical conferences in 2025. We are immensely grateful to the patients, study staff and principal investigators who made the VERIFY study possible.” Patients with PV are at increased risk for life-threatening cardiovascular and thrombotic events. Many patients with PV require regular phlebotomy, a process of removing blood to manage elevated hematocrit levels caused by an excess of red blood cells, as well as treatment with cytoreductive therapies. Phlebotomy can be burdensome and exacerbate symptoms, including severe fatigue, visual disturbances and iron deficiency, which impact patients’ quality of life. The reduction of hematocrit below 45% is a primary treatment goal for patients with PV as recommended by current treatment guidelines. “We are encouraged by these results and excited about the potential of rusfertide to help patients living with PV. These patients may experience a high treatment burden, and severe symptoms can impact their quality of life,” said Andy Plump, M.D., Ph.D., President of R&D at Takeda. “We are deeply committed to bringing additional treatment options to those living with blood cancers, including myeloid cancers such as PV.” “The totality of impressive clinical data to date shows that rusfertide has the potential for meaningful positive impact on the lives of patients with PV,” said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. “We look forward to working with our partner, Takeda, to submit our findings to the regulatory agencies. Today’s study results also mark a critical inflection point in Protagonist’s decade long journey in the hepcidin program and further validates our platform and expertise in innovating highly differentiated peptide-based medicines to fulfill unmet medical needs.” Under the license and collaboration agreement between Protagonist and Takeda, Protagonist earns a $25 million milestone payment following these positive results. The milestone is payable following completion of the VERIFY clinical study report. The impact on Takeda’s financial results for the fiscal year ending March 31, 2025 (FY2024), following the study results, is immaterial. Protagonist will host a conference call and webcast, for which details can be found below. Protagonist Investor Conference Call and Webcast Details The dial-in numbers for Protagonist’s investor update on Monday, March 3rd at 8:30 am ET are: US-based Investors: 1-877-300-8521 International Investors: 1-412-317-6026 Conference Call ID: 1793905 The webcast link for the event can be found here: https://viavid.webcasts.com/starthere.jsp?ei=1708360&tp_key=94f2832555 A replay of the presentation will be available on the Protagonist Investor Relations Events and Presentations webpage following the event. About VERIFY The Phase 3 VERIFY trial (NCT05210790) is an ongoing, three-part, global, randomized, placebo-controlled trial evaluating rusfertide in 293 patients with polycythemia vera over a 156-week period. The trial is evaluating the efficacy and safety of once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy dependent despite standard of care treatment, which could include hydroxyurea, interferon and/or ruxolitinib. The primary endpoint of the study was the proportion of patients achieving a response during weeks 20-32, which was defined as the absence of “phlebotomy eligibility.” To meet phlebotomy eligibility, patients in the study were required to have: confirmed hematocrit ≥45% that was ≥3% higher than their baseline hematocrit value, or hematocrit ≥48%. All patients have completed their participation in the randomized, placebo-controlled portion of the trial evaluating the efficacy and safety of rusfertide plus current treatment versus placebo plus current treatment and are now in the open-label portions of the trial. About Protagonist Protagonist Therapeutics is a discovery through late-stage development biopharmaceutical company. Two novel peptides derived from Protagonist’s proprietary discovery platform are currently in advanced Phase 3 clinical development, with New Drug Application submissions to the FDA expected in 2025. Icotrokinra (formerly, JNJ-2113) is a first-in-class investigational targeted oral peptide that selectively blocks the Interleukin-23 receptor (“IL-23R”) which is licensed to JNJ Innovative Medicines (“JNJ”), formerly Janssen Biotech, Inc. Following icotrokinra’s joint discovery by Protagonist and JNJ scientists pursuant to the companies’ IL-23R collaboration, Protagonist was primarily responsible for development of icotrokinra through Phase 1, with JNJ assuming responsibility for development in Phase 2 and beyond. Rusfertide, a mimetic of the natural hormone hepcidin, is currently in Phase 3 development for the rare blood disorder polycythemia vera (PV). Rusfertide is being co-developed and will be co-commercialized with Takeda Pharmaceuticals pursuant to a worldwide collaboration and license agreement entered into in 2024 under which the Company remains primarily responsible for development through NDA filing. The Company also has a number of pre-clinical stage oral drug discovery programs addressing clinically and commercially validated targets, including IL-17 oral peptide antagonist PN-881, oral hepcidin program, and oral obesity program. More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company’s website at www.protagonist-inc.com . About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com . 1 A responder is a patient who completed weeks 0-32 of the study, was not phlebotomy eligible and did not receive a phlebotomy during weeks 20-32. To meet phlebotomy eligibility, patients in the study were required to have: confirmed hematocrit ≥45% that was ≥3% higher than their baseline hematocrit value, or hematocrit ≥48%. See “About VERIFY” section. 2 Proportion of patients with hematocrit less than 45%. 3 Mean change from baseline to week 32 using PROMIS Fatigue SF-8a, a questionnaire that measures patient-reported fatigue symptoms and their impact on daily life. 4 Mean change from baseline to week 32 using MFSAF TSS-7 v. 4.0, a questionnaire that measures patient reporting of seven key symptoms related to myelofibrosis (many of which are common among PV patients as well). SOURCE: Takeda Pharmaceutical Co

Dive Brief:An injectable drug developed by Protagonist Therapeutics and Takeda Pharmaceutical met the goals of a Phase 3 study testing it in a rare blood disorder, likely setting up the companies to discuss an approval application with regulators.Results released by the companies Monday showed that significantly more participants in the study responded to the companies drug, called rusfertide, than did placebo. Specifically, researchers measured the proportion of patients who no longer needed phlebotomy, a procedure done to remove excess red blood cells.Rusfertide is designed to treat polycythemia vera, a cancer in which red blood cells proliferate and cause blood clots and other cardiovascular problems. Nearly 300 patients with uncontrolled polycythemia vera were enrolled in the companies trial, called Verify. Patients in both groups continued to receive standard therapy.Dive Insight:The positive results for rusfertide are the second Phase 3 success for a drug developed by Protagonist, which in November reported a psoriasis pill its developing with Johnson & Johnsonalso met its trial goals. Protagonist shares rose by as much as 13% Monday before falling back to trade up 3% by mid-morning.Takeda paid Protagonist $300 million one year ago to gain rights outside the U.S. to rusfertide. Protagonist retained an option to co-promote rusfertide within the U.S. and share profits, should it win regulatory approval. Under the deal, Takeda owes Protagonist a $25 million milestone payment upon completion of the Phase 3 study report.We look forward to working with our partner, Takeda, to submit our findings to the regulatory agencies, said Protagonist CEO Dinesh Patel, in a statement. Todays study results also mark a critical inflection point in Protagonists decade long journey in the hepcidin program, he added, referring to the mechanism by which rusfertide is thought to work.According to the companies, 77% of study participants treated with rusfertide met the trials definition for clinical response during weeks 20 to 32, versus just 33% of those on placebo. Treatment was also associated with improved hematocrit control and better patient-reported outcomes.No new safety findings were reported, with most adverse events mild injection site reactions. Investigators found no evidence of an increased risk of cancer in rusfertide-treated participants, the companies said.Protagonist and Takeda will report these data in detail at an upcoming medical meeting and submit them to regulatory agencies.Some 100,000 to 160,000 people are estimated to have polycythemia vera in the U.S. Marked by an elevated proportion of red blood cells, the disease is often treated with the drug hydroxyurea and with phlebotomy. A few other drugs can be used, but dont specifically address this elevated hematocrit, according to Protagonist. '

SAN RAFAEL, Calif., Feb. 24, 2025 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced that the company has appointed Timothy P. Walbert, former chairman, president and chief executive officer of Horizon Therapeutics, to the company's Board of Directors, effective Feb. 24, 2025. Mr. Walbert led Horizon, a company that focused on medicines for rare diseases, from its founding in 2008 to acquisition by Amgen in 2023. Mr. Walbert is currently senior advisor, Amgen. Prior to Horizon, Mr. Walbert served as president and chief executive officer of IDM Pharma, which was acquired by Takeda in 2009, and before that held leadership positions at NeoPharm Inc. and Abbott (now AbbVie). He brings more than 30 years of industry experience across a number of pharmaceutical companies, including Pharmacia, Merck, Pfizer and Wyeth Ayerst. Mr. Walbert currently sits on the boards of directors of Sagimet Biosciences, Mirum Pharmaceuticals and Century Therapeutics. "We are very pleased to welcome Tim to our Board of Directors," said Alexander Hardy, president and chief executive officer of BioMarin. "Tim is a deeply talented and well-respected leader with significant operational expertise, who brings a wealth of insight in commercializing medicines. Over the course of his career in the biopharmaceutical industry, he is someone who has been known for always putting patients first. The combination of his business acumen and patient-centered approach make him an ideal addition to our Board." "I am pleased to join BioMarin's Board as the company works to deliver on the new strategy laid out last year focused on innovation, growth and value creation," said Mr. Walbert. "Throughout my time in the industry, I have focused on prioritizing the needs of patients and I look forward to working with BioMarin as the team advances new medicines for people with genetically defined conditions." About BioMarin BioMarin is a global biotechnology company dedicated to translating the promise of genetic discovery into medicines that make a profound impact on the life of each patient. The San Rafael, California-based company, founded in 1997, has a proven track record of innovation with eight commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin pursues treatments that offer new possibilities for patients and families around the world navigating rare or difficult-to-treat genetic conditions. To learn more, please visit www.biomarin.com. Forward-Looking Statements This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: expectations regarding the addition of Mr. Timothy P. Walbert to BioMarin's Board of Directors and BioMarin's strategy execution and advancement of new medicines. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: finalizing the appointment of Mr. Walbert, BioMarin's success in the commercialization of its commercial products, impacts of macroeconomic and other external factors on BioMarin's operations; results and timing of current and planned preclinical studies and clinical trials and the release of data from those trials; BioMarin's ability to successfully manufacture its commercial products and product candidates; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Annual Report on Form 10-K for the year ended December 31, 2024, as such factors may be updated by any subsequent reports. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise. BioMarin® is a registered trademark of BioMarin Pharmaceutical Inc. Contacts: Investors Media Traci McCarty Marni Kottle BioMarin Pharmaceutical Inc. BioMarin Pharmaceutical Inc. (415) 455-7558 (415) 218-7111 View original content to download multimedia:https://www.prnewswire.com/news-releases/biomarin-announces-appointment-of-timothy-p-walbert-to-board-of-directors-302383833.html SOURCE BioMarin Pharmaceutical Inc.