Protagonist Therapeutics, Inc.

“I think it is a little bit of a nice bubble to be in at the moment, given all that\'s going on in the world,” Takeda\'s Teresa Bitetti said.\n The first half of this year has been riddled with market volatility and geopolitical tension. But 2025’s American Society of Clinical Oncology conference largely isn’t reflecting that turmoil.In fact, despite the chill in the air, the Chicago-based five-day meeting has felt quite the opposite. Though ASCO\'s CEO Clifford Hudis, M.D., kicked off the event with a warning about the devastating impact President Donald Trump\'s massive proposed budget cuts would have on the National Institutes of Health\'s National Cancer Institute, most attendees focused in on the potential that current pipeline programs could bring to Americans with cancer.“In a fairly tumultuous world, where we just see concerns on funding and concerns on following the science, and then you come into a venue like this—it is energizing when you see the cutting-edge science and how smart some of these advancements are,” Teresa Bitetti, president of Takeda’s global oncology business unit, told Fierce Biotech at the conference. “I think it is a little bit of a nice bubble to be in at the moment, given all that\'s going on in the world,” Bitetti added.Specific to Takeda, Bitetti said the newly shared phase 3 data for the pharma’s Protagonist Therapeutics-partnered asset designed to treat a rare chronic blood disorder was also fueling her excitement.The injectable hepcidin mimetic, called rusfertide, already met the hematology trial’s main endpoint, demonstrating a 76.9% clinical response when paired with standard of care compared to a 32.9% response for those receiving standard of care alone. That finding, which was announced in March, is now supplemented by additional findings, including details on key secondary endpoints, all of which hit their target. The late-stage trial enrolled patients with polycythemia vera (PV), a disease that increases the risk of life-threatening cardiovascular and thrombotic events, and therefore boosts the chances of requiring the regular removal of blood via phlebotomy in order to manage hematocrit levels.However, only 27% of patients in the investigational treatment arm required phlebotomy over the duration of 32 weeks, compared to 78% of patients who received placebo plus the current standard of care.“If I had had this years ago when I was practicing, I think I would have just been in tears with joy,” P.K. Morrow, M.D., head of Takeda’s oncology therapeutic area unit, told Fierce. The company is now on track to submit an approval request to the FDA in the second half of Takeda\'s fiscal year, which ends March 31, 2026.“That\'s why I do love my job, it\'s not often in your career when you can bring forward a transformative medicine, and we\'re doing that,” Bitetti added. “That, to me, is super exciting and very fulfilling.”  The conference’s homebase, a sprawling convention center called McCormick Place, appears busy as ever. Fears that recent travel advisories cautioning international visitors from entering the U.S. would impact attendance seem not to have deterred global oncology leaders. A preliminary estimate from ASCO said international on-site registrations were on pace with last year, as of the second day of the conference.For Merck & Co.’s Marjorie Green, M.D., the conference remains a place to push forward with innovative cancer treatments.“Everyone is very happy with Keytruda, and we are too, but we know we can do better,” Merck’s senior vice president and head of oncology clinical development told Fierce. She cited Merck’s investigational KRAS G12C inhibitor, known as MK-1084, which the company is studying in a recently launched phase 3 for metastatic non-small cell lung cancer (NSCLC), plus a pivotal late-stage study slated to start next month in advanced colorectal cancer.In the NSCLC trial, the KRAS G12C inhibitor is being administered in combination with the company’s blockbuster PD-1 inhibitor Keytruda. The investigational duo will be compared against the standard of care in first-line metastatic nonsquamous NSCLC, which is Keytruda combined with pemetrexed and carboplatin.“So, we’re trying to get rid of chemotherapy,” Green explained. “Rewriting textbooks, that’s what we’re going to do.”And though, in the words of Fierce Pharma’s Angus Liu, this ASCO may not have “a lot of drama in the data” occurring, any chance to learn from other thought leaders and trials being presented is a golden one.“Even if a study is a negative study, you\'ve learned something important, and we build upon whatever that is,” Green said. “You\'ve answered an important question and are advancing science. We always want to advance progress for patients.”“The promise of ASCO is exciting,” she said.

NEWARK, CA, USA & OSAKA, Japan & CAMBRIDGE, MA, USA I June 01, 2025 I Protagonist Therapeutics, Inc. (“Protagonist”) ( NASDAQ:PTGX ) and Takeda ( TSE:4502/NYSE:TAK ) announced detailed results from the Phase 3, randomized, placebo-controlled VERIFY study evaluating rusfertide in patients with polycythemia vera (PV), which met the primary and all key secondary endpoints. The data will be presented as a late-breaking oral presentation at the 61 st American Society of Clinical Oncology (ASCO) Annual Meeting Plenary Session (LBA3) at 2:09 pm CDT today. PV is characterized by overproduction of red blood cells (erythrocytosis), which may increase blood viscosity, or thickness, potentially resulting in life threatening thrombotic events such as stroke, deep vein thrombosis and pulmonary embolism. People with PV can experience burdensome symptoms, including severe fatigue, difficulty in concentrating, night sweats and pruritus, which may negatively impact their daily functioning and quality of life. Hematocrit is the ratio of red blood cells to total amount of blood in the body. Achieving and maintaining controlled hematocrit levels of <45% is the primary treatment goal in PV to prevent thrombotic events and alleviate symptoms, but many patients still experience uncontrolled hematocrit levels with current standard of care treatments. Rusfertide, an investigational, first-in-class hepcidin mimetic peptide therapeutic, is under evaluation in the Phase 3 VERIFY study for its potential to regulate iron homeostasis and red blood cell production to control hematocrit levels in patients with PV. In the study, patients dependent on frequent phlebotomy, with or without treatment with cytoreductive therapy, were randomized to receive once-weekly rusfertide or placebo, as an add-on to current standard of care treatment. “PV poses significant challenges for patients, including debilitating symptoms and the risk of serious thrombotic events, and hematocrit control is crucial to improving patient outcomes. The VERIFY study demonstrated that treatment with rusfertide controls hematocrit levels in phlebotomy-dependent patients, including patients receiving cytoreductive therapies,” said Dr. Andrew T. Kuykendall, M.D., VERIFY Lead Investigator and Associate Member in the Department of Hematology at Moffitt Cancer Center. “These results suggest rusfertide has the potential to become part of the standard of care treatment for patients with PV.” The study met its primary endpoint, which was the proportion of patients achieving a clinical response, defined as the absence of phlebotomy eligibility during study Weeks 20-32. Study results demonstrated 76.9% of patients treated with rusfertide plus current standard of care achieved a clinical response, compared to 32.9% in the placebo plus current standard of care group (p<0.0001). 1 The response observed in the rusfertide arm was consistent across subgroups, regardless of risk status or type of concurrent cytoreductive therapy. 1 In addition, all key secondary endpoints met statistical significance in favor of the rusfertide arm compared to the placebo arm in the VERIFY study, as follows: Rusfertide was generally well tolerated. The majority of adverse events were low grade and non-serious and no serious adverse events considered related to rusfertide were reported. There was no evidence of increased risk of cancer in patients treated with rusfertide plus current standard of care compared to patients treated with placebo plus current standard of care at the time of the primary analysis. Cancer events were reported in one patient in the rusfertide arm (0.7%) and in seven patients in the placebo arm (4.8%). The most common treatment-emergent adverse events were localized injection site reactions (55.9%), anemia (15.9%) and fatigue (15.2%). 1 “These findings underscore rusfertide’s potential as a first-in-class erythrocytosis-specific treatment for PV and validate more than a decade of scientific innovation originating from Protagonist’s peptide technology platform,” said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. “We would like to thank all the patients, study staff and investigators for participating in the VERIFY study. We are pleased to partner with Takeda as we continue to advance rusfertide to potentially transform the standard of care in PV patients around the world.” “These promising pivotal data strongly support rusfertide’s potential benefit for a broad spectrum of patients with PV who may be receiving current standard of care therapies but not achieving adequate hematocrit control,” said Phuong Khanh (P.K.) Morrow, M.D., Head of the Oncology Therapeutic Area Unit (OTAU) at Takeda. “We look forward to receiving additional data from the VERIFY trial later this year, advancing rusfertide towards regulatory approval and continuing our collaboration with Protagonist to bring this innovative therapy to patients.” Rusfertide has received Orphan Drug designation and Fast Track designation from the U.S. Food & Drug Administration (FDA). Takeda Investor Conference Call and Webcast Details Takeda will host an investor call regarding this update on Sunday, June 1, 6-6:45 pm CDT/ 7-7:45 pm EDT / Monday, June 2, 08:00-08:45 (JST). The call will be held using the Zoom platform and Zoom simultaneous interpretation function. Kindly pre-register from the below link: https://zoom.us/webinar/register/WN_rNp8tpIiRsemQRawBCDRMA#/registration An on-demand replay will be made available on Takeda’s website after the conclusion of the event. Protagonist Investor Conference Call and Webcast Details The dial-in numbers for Protagonist’s investor update on Monday, June 2nd at 5:00-6:00 am PDT/ 8:00-9:00 am EDT are: The webcast link for the event can be found here: https://viavid.webcasts.com/starthere.jsp?ei=1718556&tp_key=360d3b714d 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 study (NCT05210790) is an ongoing, three-part, global, randomized, placebo-controlled study evaluating rusfertide in 293 patients with polycythemia vera over a 156-week period. The study is evaluating the efficacy and safety of once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy-dependent despite current 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 study evaluating the efficacy and safety of rusfertide plus current standard of care versus placebo plus current standard of care and are now in the open-label portions of the study. 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, an oral hepcidin program, and an 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 . SOURCE: Takeda Pharmaceutical Co

Aiming to establish a new standard of care that could replace phlebotomy in treating polycythemia vera (PV), Takeda and Protagonist Therapeutics unveiled detailed findings from a Phase III study of their investigational hepcidin mimetic rusfertide at the American Society of Clinical Oncology (ASCO) annual meeting on Sunday.Top-line results from the 156-week VERIFY trial involving 293 phlebotomy-dependent patients were reported in March. The primary goal was achieved, with 76.9% of rusfertide-treated patients showing a response — defined as absence of phlebotomy eligibility — during weeks 20-32, versus 32.9% on placebo. The trial also met a key secondary goal — which is also the EU regulatory primary endpoint, with the rusfertide group averaging 0.5 phlebotomies per patient versus 1.8 in the placebo group during weeks 0-32. Additional data on secondary endpoints were presented at ASCO, with the partners noting that 27% of rusfertide-treated patients required phlebotomy compared with 78% receiving placebo. Furthermore, haematocrit control — a vital treatment goal in PV — showed significant improvement, with 62.6% of rusfertide recipients maintaining levels below 45% versus 14.4% of placebo recipients. Significant improvements at week 32 were also obeserved on PROMIS Fatigue2 and MFSAF Total Symptom Score (both p< 0.03)."These promising pivotal data strongly support rusfertide's potential benefit for…patients…who may be receiving current standard of care therapies but not achieving adequate haematocrit control," said Phuong Khanh Morrow, head of Takeda's oncology therapeutic area unit.With efficacy firmly established, analysts had their eyes glued on the drug’s safety, which was sparsely discussed in the top-line readout. Rusfertide demonstrated favourable tolerability with no serious adverse events (AEs) attributed to treatment. Cancer events were reported in one rusfertide recipient (0.7%) and seven placebo recipients (4.8%). The most common treatment-emergent AEs included localised injection site reactions (55.9%), anaemia (15.9%), and fatigue (15.2%). The companies anticipate additional data from VERIFY later this year to support regulatory filings.