rusfertide (PTG-300) / Protagonist Therap, Takeda - LARVOL DELTA

Novel Therapies in Essential Thrombocythemia and Polycythemia Vera (SOHO 2025) - P1, P1/2, P2, P3 | "In PV, recommended cytoreductive options include hydroxyurea, pegIGN, ropeginterferon-alpha-2b (ropeginterferon), and ruxolitinib...A novel fully human IgG1 monoclonal antibody against mutant CALR (INCA033989) has demonstrated promising preclinical activity...Another phase 1 trial evaluating JNJ-88549968, a novel bispecific antibody that binds to both mutant CALR and T cells to enhance cytotoxicity, 10 is also enrolling both CALR -mutated ET and MF patients (NCT06150157)...12 A phase 2 trial of bomedemstat in high-risk ET patients who were resistant or intolerant to hydroxyurea demonstrated that 94% (34/36) of patients met hematologic response criteria after a median of 8 weeks, with stable hemoglobin levels and improved white blood cell counts...Novel Therapies in Polycythemia Vera Rusfertide and Hepcidin Mimetics Maintenance of a hematocrit <45% is a core aspect of PV therapy, which can be accomplished with a combination of therapeutic phlebotomy..."

IO biomarker • Chronic Myeloid Leukemia • Essential Thrombocythemia • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • CALR • JAK2 • KLK7 • MPL • TMPRSS6

Results From VERIFY, an International, Randomized, Phase 3, Double-Blind, Placebo-Controlled Study of Rusfertide (First-in-Class Hepcidin Mimetic) for Treatment of Polycythemia Vera (PV) (SOHO 2025) - P3 | "Rusfertide resulted in a statistically significant reduction in the mean number of phlebotomies, improved hematocrit control, and statistically significant improvements in the PROMIS Fatigue SF-8a and MFSAF in patients with PV."

Clinical • P3 data • Myelofibrosis • Oncology • Polycythemia Vera

Rusfertide Receives Breakthrough Therapy Designation for Treatment of Erythrocytosis in Patients with Polycythemia Vera (ACCESS Newswire) - "Breakthrough designation for rusfertide was supported by positive 32-week data from the Phase 3 VERIFY study..."

Breakthrough therapy • Polycythemia Vera

Hepcidin Mimetic in Patients With Polycythemia Vera (REVIVE) (clinicaltrials.gov) - P2 | N=70 | Completed | Sponsor: Protagonist Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Polycythemia Vera

VERIFY: A Phase 3 Study of Rusfertide in Patients With Polycythemia Vera (clinicaltrials.gov) - P3 | N=293 | Active, not recruiting | Sponsor: Protagonist Therapeutics, Inc. | Trial completion date: Jun 2025 ➔ Jun 2027

Trial completion date • Polycythemia Vera

THRIVE: Study to Evaluate the Long-term Safety of Rusfertide (PTG-300) in Subjects With Polycythemia Vera (clinicaltrials.gov) - P3 | N=46 | Active, not recruiting | Sponsor: Protagonist Therapeutics, Inc. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Polycythemia Vera

Protagonist Reports Second Quarter 2025 Financial Results and Provides Corporate Update (ACCESS Newswire) - "Second Quarter 2025 Recent Developments and Upcoming Milestones:...Rusfertide U.S. NDA filing for treatment of patients with PV, by partner Takeda Pharmaceuticals, expected in Q4 of this year."

FDA filing • Polycythemia Vera

Results from VERIFY, a phase 3, double-blind, placebo (PBO)-controlled study of rusfertide for treatment of polycythemia vera (PV). (BASCO-MN 2025) - No abstract available

Clinical • Late-breaking abstract • P3 data • Polycythemia Vera

Results from VERIFY, a phase 3, double-blind, placebo (PBO)-controlled study of rusfertide for treatment of polycythemia vera (PV). (ASCO 2025) - P3 | "In pts with PV receiving SOC, rusfertide resulted in a statistically significant reduction in the mean number of PHLs and improved Hct control. Rusfertide is the first investigational agent to target the hepcidin pathway to control Hct and the first agent to prospectively demonstrate a statistically significant improvement in the PROMIS Fatigue SF-8a and MFSAF PROs in pts with PV. Rusfertide had a safety and tolerability profile consistent with rusfertide in prior studies."

Clinical • Late-breaking abstract • P3 data • Anemia • Fatigue • Polycythemia Vera

Rusfertide: Presentation of data from P3 VERIFY trial (NCT05210790) for polycythemia vera at ASH (Dec 6-9, 2025) (Protagonist Therapeutics) - ASCO 2025

P3 data • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Rusfertide: “VERIFY study met its primary endpoint during weeks 20-32 (Part 1a)”; Polycythemia vera (Protagonist Therapeutics) - ASCO 2025: “Significantly reduced the mean number of PHL and improved Hct control in the desired target range (Hct < 45%) vs. placebo”

P3 data • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Moffitt to Present Plenary and Late-Breaking Data on Blood, Melanoma and Brain Metastases at ASCO 2025 (Newswise) - "Moffitt will be prominently featured at this year’s ASCO Annual Meeting, including a plenary presentation on polycythemia vera. Additional highlights include several oral presentations on melanoma, renal cell carcinoma and head and neck squamous cell carcinoma. Moffitt researchers will also present multiple posters covering a wide range of cancer types, including lung, breast, cervical and biliary tract cancers."

Clinical data • Biliary Tract Cancer • Breast Cancer • Cervical Cancer • Cholangiocarcinoma • Clear Cell Renal Cell Carcinoma • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Polycythemia Vera • Squamous Cell Carcinoma of Head and Neck

Protagonist and Takeda Announce ASCO Plenary Presentation Highlighting Full 32-Week Results from Phase 3 VERIFY Study of Rusfertide, Showing Reductions in Phlebotomy, Improved Hematocrit Control in Polycythemia Vera (Businesswire) - P3 | N=250 | VERIFY (NCT05210790) | Sponsor: Protagonist Therapeutics, Inc. | "Rusfertide plus current standard of care more than doubled clinical response rates across high- and low-risk PV groups, significantly reducing phlebotomy eligibility compared to placebo plus current standard of care, which was the primary endpoint; All key secondary endpoints met with statistical significance, including a nearly three-fold reduction in the proportion of patients requiring phlebotomy and a four-fold improvement in hematocrit control in rusfertide arm compared to placebo arm, as well as improvements in patient-reported outcomes;No serious adverse events considered related to rusfertide were reported."

P3 data • Polycythemia Vera

Protagonist Therapeutics Announces Plenary Presentation on VERIFY Phase 3 Study with Rusfertide at ASCO 2025 (ACCESSWIRE) - "Protagonist Therapeutics...announced that an abstract was accepted for presentation at the Plenary Session at the American Society of Clinical Oncology (ASCO) Annual Meeting....Presentation Details:...Title: Results From VERIFY, a Phase 3, Double-Blind, Placebo (PBO)-Controlled Study of Rusfertide for Treatment of Polycythemia Vera (PV); Abstract: LBA3;...Session Date: Sunday, June 1, 2025; Presentation Time: 2:09 PM - 2:21 PM CDT."

P3 data • Polycythemia Vera

Rusfertide: “Study met primary endpoint with a significantly higher proportion of clinical responders on rusfertide compared to placebo during weeks 20-32 (p<0.0001)”; Polycythemia Vera (Protagonist Therapeutics) - Investor Call and Webcast: “Phlebotomy rate - EU primary endpoint (p<0.0001)”

P3 data: top line • Hematological Malignancies • Oncology • Polycythemia Vera

Protagonist and Takeda Announce Positive Topline Results from Phase 3 VERIFY Study of Rusfertide in Patients with Polycythemia Vera (Businesswire) - P3 | N=250 | VERIFY (NCT05210790) | Sponsor: Protagonist Therapeutics, Inc. | "The primary endpoint of the study was met, with a significantly higher proportion of clinical responders among rusfertide-treated patients with PV (77%) compared to those who received placebo (33%) during weeks 20-32; p<0.0001....The first key secondary endpoint, which is the pre-specified primary endpoint for European Union (EU) regulators, was also met, with a mean of 0.5 phlebotomies per patient in the rusfertide arm compared to 1.8 phlebotomies per patient in the placebo arm during weeks 0-32; p<0.0001....'We plan to submit additional details of these promising results for presentation at upcoming medical conferences in 2025'....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."

Financing • P3 data • Polycythemia Vera

Rusfertide: Regulatory submission in US for polycythemia Vera (based on VERIFY trial) in Q4 2025 (Protagonist Therapeutics) - Corporate Presentation

FDA filing • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Takeda Delivers Strong Third-Quarter FY2024 Results; Raises Full Year Outlook, Forecasting Revenue and Core Operating Profit Margin Growth (Businesswire) - "Takeda...announced earnings results for the third quarter of fiscal year 2024 (nine months ended December 31, 2024) showing continued advancement of its Growth & Launch Products, which delivered double-digit growth of 14.6% at CER....Among the multiple late-stage programs presented, the company expects...Phase 3 data readouts in the calendar year 2025 with filings anticipated in FY2025-FY2026 for the following program...rusfertide for the treatment of polycythemia vera, a rare chronic blood disorder; additional indication filings for late-stage programs are on pace for FY2027-FY2029....elritercept for the treatment of anemia associated with myelodysplastic syndrome"

Commercial • Filing • P3 data • Anemia • Myelodysplastic Syndrome • Polycythemia Vera

Protagonist Therapeutics Receives FDA Breakthrough Therapy Designation for Rusfertide in Polycythemia Vera (PRNewswire) - "Protagonist Therapeutics...announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for its lead investigational new drug candidate, rusfertide, for the treatment of patients with polycythemia vera (PV) for the reduction of erythrocytosis in those patients who do not require further treatment for thrombocytosis and/or leukocytosis."

Breakthrough therapy • Polycythemia Vera

Multiple-Dose Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Subcutaneous Rusfertide, a Hepcidin Mimetic, in Healthy Subjects. (PubMed, Clin Pharmacol Drug Dev) - "While a higher incidence of treatment-emergent adverse events was noted in these healthy participants following multiple doses of 60 mg, rusfertide was generally well tolerated. There were no clinically meaningful differences in rusfertide pharmacokinetics or pharmacodynamics between injection sites."

Journal • PK/PD data • Dermatology • Fatigue • Pain • Polycythemia Vera • Pruritus

Rusfertide: 32-week primary endpoint data from P3 VERIFY trial (NCT05210790) for polycythemia vera in March 2025 (Protagonist Therapeutics) - Corporate Presentation

P3 data • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Takeda Spotlights High-Value, Late-Stage Pipeline Accelerating the Development of Potential Transformative Treatments for Patients in Multiple Therapeutic Areas (Businesswire) - "Expected Phase 3 Data Readouts in 2025 for...Rusfertide (TAK-121); Regulatory Filings for...Rusfertide (Polycythemia Vera) on Track for Fiscal Years 2025 - 2026; Five Additional Filings Anticipated in Fiscal Years 2027 - 2029 Including First Indication Submissions for...Elritercept (TAK-226)....elritercept, an investigational activin inhibitor designed to treat anemia associated with certain hematologic cancers, including myelodysplastic syndromes (MDS)."

FDA filing • P3 data • Myelodysplastic Syndrome • Oncology • Polycythemia Vera

Final Results from the Phase 2 Revive Study Investigating the Hepcidin Mimetic Rusfertide in Patients with Polycythemia Vera (PV) (ASH 2024) - P2, P3 | "Patients are eligible to roll over to the phase 2 THRIVE OLE study (NCT06033586), which will continue to assess the long-term safety and efficacy of rusfertide for a total period of up to 5.8 years. The randomized phase 3 VERIFY study (NCT05210790) is ongoing and will evaluate rusfertide vs placebo in PV patients."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Dermatology • Fatigue • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Musculoskeletal Pain • Myeloproliferative Neoplasm • Novel Coronavirus Disease • Oncology • Pain • Polycythemia Vera • Pruritus • Skin Cancer • CRP • IL6

Rusfertie: “In REVIVE, rusfertide added to TP with or without CRT controlled erythrocytosis, provided long-term durable control of Hct, and decreased the need for TP in patients with PV”; Polycythemia vera (Protagonist Therapeutics) - ASH 2024: “Rusfertide was well-tolerated; the most common adverse events were Grade 1 or 2 injection site reactions, fatigue, pruritus, COVID-19, arthralgia, dizziness, nausea, headache, anemia, paresthesia, and diarrhea”

P2 data • Hematological Malignancies • Oncology • Polycythemia Vera

Protagonist Reports Final Results From Rusfertide Phase 2 REVIVE Study Showing Durable Hematocrit Control at the ASH 2024 Annual Meeting (ACCESSWIRE) - P2 | N=80 | REVIVE (NCT04057040) | Sponsor: Protagonist Therapeutics, Inc. | "Final results show that rusfertide, when added to therapeutic phlebotomy with or without cytoreductive therapy achieved long term durable control of hematocrit below the 45% threshold for over 3 years. Prior to enrollment, the estimated mean phlebotomy rate (EPHL) in patients who enrolled on study was >5/year: In Part 1, the EPHL was <1/year in patients who received rusfertide (N=70). In Part 2 (randomized withdrawal phase), the EPHL was <1/year and approximately 6.1/year in the rusfertide and placebo groups, respectively. For patients who continued to Part 3 (Week 42+), the EPHL remained at <1/year....Overall, 18 (26%) patients experienced serious adverse events (SAEs); most SAEs were unrelated and likely associated with the underlying disease. One patient developed acute myeloid leukemia after treatment discontinuation."

P2 data • Polycythemia Vera