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

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

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

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

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

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

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

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

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

Rusfertide rapidly decreases hematocrit in patients with suboptimally controlled polycythemia vera. (PubMed, Leuk Res) - "In this open-label phase 2 study, rusfertide resulted in a rapid and sustained improvement in hematocrit and was generally well tolerated. Rapid and sustained control of hematocrit reduces the need for therapeutic phlebotomy and may help reduce thrombotic and cardiovascular events over the long term in patients with PV."

Journal • Cardiovascular • Hematological Disorders • Polycythemia Vera

Takeda Reports First Half FY2025 Results, with Business Fundamentals Tracking as Planned. Updates Full Year Outlook to Reflect FX Impact and Pipeline Impairment. On Track for Multiple Regulatory Filings This Fiscal Year (FinancialContent) - "First Half Revenue Declined 3.9% at Constant Exchange Rate (CER), -6.9% at Actual Exchange Rates (AER), Impacted by Generic Erosion of VYVANSE and FX Headwind...'We see FY2025 as a pivotal year for Takeda with regulatory filings for rusfertide and oveporexton expected in the second half of the year, as well as Phase 3 results for zasocitinib.'"

Commercial • Filing • P3 data • CNS Disorders • Polycythemia Vera • Psoriatic Arthritis

Results From VERIFY, a Phase 3, Double-Blind, Placebo (PBO)-Controlled Study of Rusfertide for Treatment of Polycythemia Vera (PV) (JADPRO 2025) - "INTRODUCTION Tecclistamab is the first and only approved bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3. These results support further exploration of prophylactic tocilizumab to reduce the incidence and/or severity of talquetamab-related CRS in the first full treatment dose. KEY TAKEAWAY A single tocilizumab dose before the first teclistamab IV dose and daily dexamethasone for 48 hours after talquetamab step-up and first full treatment doses reduced CRS incidence and severity versus the overall MonumenTAL-1 population."

Clinical • P3 data • Infectious Disease • Inflammation • Polycythemia Vera

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

Johnson & Johnson in talks to acquire Protagonist Therapeutics, source says (Reuters) - "Shares of Protagonist surged more than 30% in afternoon trading. The company had a market capitalization of $4.2 billion as of Thursday's close....Protagonist is also developing rusfertide, a late-stage blood cancer drug candidate, with Takeda Pharmaceutical."

M&A • Stock price • Polycythemia Vera

Evaluation of Rusfertide, a Hepcidin Mimetic, on Cardiac Repolarization: A Randomized, Placebo- and Positive-Controlled Crossover Thorough QT Study in Healthy Participants. (PubMed, Clin Ther) - "Rusfertide had no clinically relevant effect on HR, cardiac conduction, or QTc. Rusfertide was well tolerated. An effect on ΔΔQTcF exceeding 10 ms could be excluded within the observed rusfertide plasma concentrations up to approximately 2130 ng/mL."

Clinical • Journal • Dermatology • Infectious Disease • Influenza • Pain • Respiratory Diseases

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