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

Long-term rusfertide treatment in polycythemia vera: Initial results from the phase 2 THRIVE extension study (ASH 2025) - P2, P3 | "After transitioning to THRIVE, continued treatment with rusfertide with or without CRTdemonstrated consistent, long-term Hct control with reduced therapeutic PHLs compared to baseline.With a median of 3.8 years of treatment, rusfertide's safety profile was consistent with priorobservations.Support: Protagonist Therapeutics, Inc."

P2 data • Basal Cell Carcinoma • Bladder Cancer • Dermatology • Genito-urinary Cancer • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Musculoskeletal Pain • Non-melanoma Skin Cancer • Polycythemia Vera • Pruritus • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma

Potential Rusfertide Approval May Offer More Control of Polycythemia Vera (Cancer Network) - "Following the agency's regulatory decision, CancerNetwork spoke with Kuykendall...about what the potential approval of rusfertide would mean for patients with polycythemia vera. He highlighted how data from studies like the phase 3 VERIFY trial (NCT05210790) affirm rusfertide’s ability to control hematocrit in this population. Additionally, he detailed the potential next steps for determining the benefit of rusfertide in other polycythemia vera subgroups and described other hepcidin-targeting agents in the pipeline that may help improve patient outcomes."

Media quote • Regulatory

Modulators of the Hepcidin Pathway in Polycythemia Vera and Myelofibrosis. (PubMed, Blood) - "Since hepcidin levels are relatively low in PV patients, hepcidin agonists (rusfertide, divesiran, sapablursen) are undergoing clinical development to control PV associated erythrocytosis, thereby reducing the need for therapeutic phlebotomies and myelosuppressive therapeutic options. A number of strategies to lower hepcidin levels (the JAK2 inhibitors pacritinib and momelotinib, anti-hemojuvelin monoclonal antibody DISC-0974C) are currently undergoing clinical development to make systemic iron available for erythropoiesis and alleviate the degree of MF associated anemia. These new therapeutic options that modulate iron trafficking in PV and MF patients represent the application of greater knowledge of iron trafficking to create novel therapeutic options to treat patients with hematological malignancies."

Journal • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Myelofibrosis • Oncology • 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 or placebo plus current standard-of-care therapy for polycythemia vera: Durability of response and safety results through week 52 from the randomized controlled phase 3 VERIFY study (ASH 2025) - P3 | "Rusfertide met the primary and all 4 key secondary endpoints in VERIFY and continued toprovide durable, sustained control of Hct <45% and a relative absence of PHL up to Wk 52. This benefitwas maintained across all subgroups, including age, PV risk category, and ongoing CRT. Similar findingswere also observed after pts crossed over from PBO to rusfertide."

Clinical • P3 data • Polycythemia Vera

Takeda and Protagonist Announce U.S. Food and Drug Administration Accepts New Drug Application and Grants Priority Review for Rusfertide as a Potential First-in-Class Therapy for Polycythemia Vera (Takeda Press Release) - "The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date in the third quarter of this calendar year....The NDA for rusfertide was primarily based on the positive 32-week primary analysis and 52-week results from the Phase 3 global randomized VERIFY study (NCT05210790), as well as four-year efficacy and safety data from the Phase 2 REVIVE study (NCT04057040) and long-term extension THRIVE study (NCT06033586)."

FDA approval • FDA filing • Priority review • Polycythemia Vera

Protagonist…Provides Corporate Update (ACCESS Newswire) - "NDA for rusfertide submitted to the US Food and Drug Administration (FDA), with potential approval and launch this year. Company expects to opt-out of the 50:50 profit and loss sharing arrangement for rusfertide with Takeda during a 90-day window expected to open in Q2."

Commercial • FDA approval • Launch US • Polycythemia Vera

UPDATED LONG-TERM RESULTS FROM THE PHASE 2 REVIVE STUDY INVESTIGATING THE HEPCIDIN MIMETIC RUSFERTIDE IN POLYCYTHEMIA VERA PATIENTS (PTS): HEMATOCRIT CONTROL AND THERAPEUTIC PHLEBOTOMY (TP) FREQUENCY (EHA 2024) - P2, P3 | "In REVIVE, rusfertide added to TP with or without CRT provided long-term durable control of Hct anddecreased the need for TP compared with the pre-study period. REVIVE pts are eligible to roll over to the open-label phase 2 extension THRIVE study (NCT06033586), which will continue to assess the long-term safety andefficacy of rusfertide. The randomized phase 3 VERIFY study (NCT05210790) is also ongoing to evaluaterusfertide vs."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Dermatology • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Musculoskeletal Pain • Novel Coronavirus Disease • Oncology • Pain • Polycythemia Vera • Pruritus

Rusfertide (Ptg-300) Treatment Interruption Reverses Hematological Gains and Upon Reinitiation, Restoration of Clinical Benefit Observed in Patients With Polycythemia Vera (SOHO 2022) - P2, P3 | "Rusfertide maintains HCT at <45%, essentially eliminates TP requirements, and reverses iron defi ciency in PV patients with/without cytoreductive agents. Reversal of hematological parameters during dosing interruption further confi rms the effect of rusfertide on erythrocytosis and iron homeostasis. A global Phase 3 trial, VERIFY (NCT05210790), has been initiated."

Clinical • 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 • Oncology • Pain • Polycythemia Vera • Pruritus • Skin Cancer • CRP • IL6

TARGETED THERAPY OF UNCONTROLLED ERYTHROCYTOSIS IN POLYCYTHEMIA VERA WITH THE HEPCIDIN MIMETIC, RUSFERTIDE: - BLINDED RANDOMIZED WITHDRAWAL RESULTS OF THE REVIVE STUDY (EHA 2023) - P2 | "The randomized withdrawal phase of the REVIVE study met its primary endpoint and demonstrated that rusfertide is a highly effective agent in patients with PV receiving TP with or without CYTO. Rusfertide is a novel hepcidin mimetic that selectively targets uncontrolled erythrocytosis in PV. Rusfertide is well tolerated and produces sustained and durable HCT control, obviating the need for TP in PV patients."

Clinical • Late-breaking abstract • Cardiovascular • Hematological Disorders • Polycythemia Vera

Durability of Hematocrit Control in Polycythemia Vera with the First-in-Class Hepcidin Mimetic Rusfertide: Two-Year Follow up Results from the Revive Study (ASH 2023) - P2 | "The REVIVE OLE demonstrated that rusfertide can provide long-term control of HCT, without phlebotomy, in patients with PV receiving TP with or without CYTO. Ferritin improved with rusfertide dosing and other lineages, after an initial increase in platelet counts both platelets and leucocyte counts remained stable during rusfertide treatment. Rusfertide was added to the current standard of care and was generally well-tolerated; most TEAEs were grade 1 or 2."

Cardiovascular • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Rusfertide: Launch for polycythemia vera (based on VERIFY trial) in H2 2026 (Takeda) - Q3 FY2025 Results

Launch • Hematological Malignancies • Oncology • Polycythemia Vera

Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera. (PubMed, N Engl J Med) - P2 | "In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040.)."

Journal • Chronic Eosinophilic Leukemia • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Subgroup Analysis of Adverse Events Following Rusfertide Dosing in Revive: A Phase 2 Study of Patients with Polycythemia Vera (ASH 2022) - P2 | "Consistent with previous reports [Pemmaraju, Blood 2019], secondary malignancies (6 early-stage skin cancers and 1 AML) were observed in 5 patients, all with prior history of malignancy or cytoreductive therapy. These data suggest that the rusfertide TEAE profile is manageable across the range of PV patients."

Adverse events • Clinical • P2 data • Acute Myelogenous Leukemia • Cardiovascular • Fatigue • Genetic Disorders • Hematological Disorders • Non-melanoma Skin Cancer • Polycythemia Vera • Pulmonary Disease • Skin Cancer • Solid Tumor • Thrombocytosis • Thrombosis

Takeda…and Protagonist Therapeutics…have submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration seeking approval for rusfertide to treat adults with polycythemia vera (PV) (Investing.com) - "The NDA submission includes 52-week data from the Phase 3 VERIFY study, which met its primary endpoint and all four key secondary endpoints."

FDA filing • Polycythemia Vera

Comprehensive analyses of patient-reported outcomes from the phase 3 VERIFY study of rusfertide or placebo plus current standard of care for polycythemia vera (ASH 2025) - P3 | "In VERIFY, the first phase 3 study in PV to prospectively investigate PROs as key secondaryendpoints, rusfertide led to statistically significant improvements vs PBO in patient-reported symptoms.Rusfertide significantly reduced fatigue and overall symptom burden (PROMIS Fatigue SF-8a and MFSAFTSS7 scores) and resulted in significant improvements from BL (p<0.05) in pts with moderate-to-severesymptoms at BL in core PV symptoms (MFSAF TSS4) and problems with concentration (MPN-SAF) vs PBO.In the rusfertide group, more pts improved by ≥1 severity category in the PROMIS Fatigue SF-8a andMFSAF TSS7 vs PBO. Overall, these results confirm the robustness of rusfertide's clinical benefit in PV,particularly in pts with moderate or severe symptoms at BL.Support: Protagonist Therapeutics, Inc."

Clinical • P3 data • Patient reported outcomes • Dermatology • Hematological Disorders • Musculoskeletal Pain • Myeloproliferative Neoplasm • Polycythemia Vera • Pruritus

Should dermatologic examinations become routine standard of care in patients with polycythemia vera? Observations from the phase 3 VERIFY study prior to rusfertide exposure (ASH 2025) - P3 | "Of these 11 patients, 9(81.8%) received hydroxyurea (HU), 2 (18.2%) received interferon, and 1 (9.1%) received ruxolitinib priorto being screened for their potential participation in VERIFY (3/11 patients received more than one priorcytoreductive therapy [CRT]). To our knowledge, this is the first phase 3 study in the setting of PV to prospectively screenpatients for skin cancers prior to being exposed to the investigational agent under study. Identification ofnon-malignant and malignant skin lesions in VERIFY prior to rusfertide exposure illustrates theimportance of screening patients with PV for these lesions. Routine dermatologic screening deservesfurther investigation in other clinical studies and as a potential SOC for optimal treatment andmanagement of patients with PV.Supported by: Protagonist Therapeutics, Inc."

Clinical • P3 data • Actinic Keratosis • Basal Cell Carcinoma • Bowens Disease • Dermatology • Dermatopathology • Genetic Disorders • Hematological Malignancies • Leukemia • Melanoma • Non-melanoma Skin Cancer • Polycythemia Vera • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Protagonist Therapeutics…and Takeda…announce that new 52-week results from the pivotal Phase 3 VERIFY study evaluating rusfertide in patients with polycythemia vera (PV) will be presented in an oral presentation at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition (Takeda Press Release) - "61.9% of patients treated with rusfertide plus current standard of care throughout Parts 1a and 1b of the study experienced a durable clinical response, defined as absence of phlebotomy eligibility. 84.1% of patients treated with rusfertide who experienced a clinical response in the Part 1a assessment window (Weeks 20-32) maintained their response. 77.9% of patients who crossed over from placebo to rusfertide at Week 32 for Part 1b experienced a clinical response during the Part 1b assessment window (Weeks 40-52)."

P3 data • Polycythemia Vera

Results From VERIFY, a Phase 3, Double-Blind, Placebo-Controlled Study of Rusfertide in Patients Receiving Current Standard-of-Care For Polycythemia Vera (PV) (MPN 2025) - No abstract available

Clinical • P3 data • Polycythemia Vera

634. Myeloproliferative Syndromes: Clinical and Epidemiological: Treatment and Outcomes in MPNs (ASH 2023) - "Hydroxyurea and pegylated interferon are common first line treatments for MPN, each with potential advantages and disadvantages...Novel therapies include hepcidin mimetic rusfertide in PV and the LSD-1 inhibitor bomedemstat in ET. In mastocytosis, the KIT inhibitor bezuclastinib shows efficacy and safety in patients with indolent mastocytosis. In myeloid neoplasms with eosinophilia, a custom NGS panel is used to explore the molecular landscape in patients negative for tyrosine kinase fusion genes, identifying recurrent JAK/STAT mutations associated with response to JAK inhibitors."

Clinical • Cardiovascular • Eosinophilia • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombocytosis • Thrombosis

Rusfertide Improves Markers of Iron Deficiency in Patients with Polycythemia Vera (ASH 2023) - P2 | "Treatment with rusfertide resulted in rapid, robust, and sustained reduction in HCT levels in PV patients with elevated HCT levels at baseline. Treatment resulted in normalization of iron parameters as noted by increases in ferritin, and normalization of serum iron and MCV in patients who were iron deficient at baseline. Improvements in iron deficiency following rusfertide are suggestive of clinical benefits and merit further investigation."

Clinical • Chronic Eosinophilic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • ERFE

Protagonist Therapeutics…announced that clinical data on rusfertide in polycythemia vera, including the Phase 3 VERIFY study, will be the focus of four presentations at the 67th Annual American Society of Hematology (ASH) Annual Meeting… (ACCESS Newswire)

Clinical data • Polycythemia Vera

Rusfertide: Regulatory approval in US for polycythemia vera (based on VERIFY trial) in Q4 2026 (Protagonist Therapeutics) - Corporate Presentation: Launch in US for polycythemia vera (based on VERIFY trial) in H1 2027

FDA approval • Hematological Malignancies • Oncology • Polycythemia Vera

Rusfertide U.S. NDA filing for treatment of patients with PV, by partner Takeda Pharmaceuticals, is expected in Q4 of this year (ACCESS Newswire)

FDA filing • Polycythemia Vera