sapablursen (ONO-0530) / Ionis, Ono Pharmaceutical, Deciphera Pharmaceuticals - LARVOL DELTA

Evaluation of the novel TMPRSS6 antisense inhibitor sapablursen for treatment of polycythemia vera: Results of the imprssion clinical trial (ASH 2025) - P2 | "Treatment of PV patients with sapablursen increased serum hepcidin, controlled Hct, reducedphlebotomy need and improved quality of life in a dose-dependent manner. These findings highlight thepotential of sapablursen as a therapeutic approach in PV and support further development."

Clinical • Hematological Disorders • Myeloproliferative Neoplasm • Polycythemia Vera • KLK7 • TMPRSS6

Sapablursen for Erythrocytosis Control in Patients with Polycythemia Vera. (PubMed, Blood) - P2 | "Sapablursen reduced phlebotomy need, improved symptoms, and was safe and well-tolerated in patients with polycythemia vera. (Funded by Ionis Pharmaceuticals; ClinicalTrials.gov: NCT05143957)."

Journal • Cardiovascular • Fatigue • Hematological Disorders • Polycythemia Vera • Thrombosis • KLK7 • TMPRSS6

Modulation of the Hepcidin Pathway Produces Homogeneous Erythropoietic Suppression but Heterogeneous Iron Repletion in Polycythemia Vera: Lessons From REVIVE and IMPRSSION (SOHO 2026) - "Agents under clinical investigation harness the hepcidin pathway to restrict iron, resulting in a "chemical phlebotomy." Rusfertide, a hepcidin mimetic, and sapablursen, a transmembrane protease serine 6 (TMPRSS6) antisense oligonucleotide that leads to increased endogenous hepcidin production, are two such emerging therapies. We showed that control of HCT is linked to an increase in ferritin when two mechanistically distinct agents modulating the hepcidin-iron axis suppress erythropoiesis in PV. Although interpatient variability in HCT was narrow, increases in ferritin levels were more heterogenous. Hence, HCT response does not reliably predict iron repletion status."

Heterogeneity • Oncology • Polycythemia Vera • TMPRSS6

ONO-0530: Launch in US/EU/Japan for polycythemia vera in FY2029 or later (Ono Pharmaceuticals) - Q1 FY2026 Results

Launch Europe • Launch Japan • Launch US • Hematological Malignancies • Oncology • Polycythemia Vera

IMPRSSION: A Study to Evaluate Sapablursen (Formerly ISIS 702843, IONIS-TMPRSS6-LRx) in Patients With Polycythemia Vera (clinicaltrials.gov) - P2 | N=50 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Polycythemia Vera

Dr Bose on the Rationale for Evaluating Sapablursen in Polycythemia Vera (OncLive) - "According to Bose, hepcidin-modulating agents have the potential to minimize or eliminate the need for phlebotomy and simultaneously provide more durable hematocrit control. He also suggested that hepcidin modulators could complement existing cytoreductive therapies rather than replace them. In this treatment paradigm, agents such as interferon or ruxolitinib could continue to target the underlying disease biology, whereas hepcidin-directed therapies address hematocrit control, together offering a more comprehensive approach to the treatment of patients with polycythemia vera."

Video

Sapablursen: Launch in US/EU for polycythemia vera in FY2028 or later (Ono Pharmaceuticals) - R&D Day

Launch Europe • Launch US • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

SUSTAINED CONTROL OF EXCESSIVE ERYTHROPOIESIS BY THE TMPRSS6 ANTISENSE INHIBITOR SAPABLURSEN IN POLYCYTHEMIA VERA: IMPRSSION TRIAL TREATMENT EXTENSION DATA (EHA 2026) - P2 | "Summary/Conclusion Hematocrit control with sapablursen was durable through 73 weeks of treatment. These findings highlight the sustained control of excessive erythropoiesis by sapablursen and establish 80 mg SC Q4W as an optimal starting dose for future studies."

Hematological Disorders • Hematological Malignancies • Peptic Ulcer • Polycythemia Vera • KLK7 • TMPRSS6

Deciphera Pharmaceuticals, LLC…announced the first patient was dosed in the global pivotal Phase 3 INTREPID study evaluating sapablursen for the treatment of polycythemia vera (PV) (FinancialContent) - "INTREPID is a pivotal global Phase 3 study in patients with phlebotomy-dependent PV designed to compare the efficacy and safety of sapablursen to placebo over a 32-week double-blind treatment period followed by up to 124 weeks of open label treatment....Durability of response will be evaluated in patients randomized to sapablursen over 52 weeks of study treatment, including 32 weeks of blinded treatment and 20 weeks of open-label treatment....The INTREPID clinical trial has initiated in the United States and is planned in additional regions including North America, Latin America, Asia Pacific and Europe."

Trial status • Polycythemia Vera

Phase 2a randomized study to evaluate sapablursen in patients with non-transfusion dependent β-thalassemia intermedia. (PubMed, Blood Adv) - P2 | "explores this mechanism in a mouse model of NTDT. Trial Registration Number: NCT04059406."

Journal • P2a data • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Polycythemia Vera • ERFE • TMPRSS6

ONO-0530: Launch in US/EU/Japan for polycythemia vera in FY2029 or later (Ono Pharmaceuticals) - FY2025 Results

Launch Europe • Launch Japan • Launch US • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

A Study of Sapablursen Evaluating the Safety and Efficacy in Participants With Polycythemia Vera (PV) (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Ono Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • 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

Ono’s Deciphera drops early-stage solid tumor drug for strategic reasons (FierceBiotech) - "DCC-3084, a pan-RAF inhibitor, 'is no longer in our pipeline and we are currently not planning additional development at this time,' a Deciphera spokesperson confirmed to Fierce Biotech on Tuesday. The decision was made for strategic reasons and unrelated to the asset’s safety or efficacy, they explained....Even with DCC-3084 sent to the scrap heap, Deciphera still boasts a packed pipeline led by BTK inhibitor tirabrutinib and antisense oligonucleotide sapablursen."

Discontinued • Solid Tumor

A Study of Sapablursen Evaluating the Safety and Efficacy in Participants With Polycythemia Vera (PV) (clinicaltrials.gov) - P3 | N=250 | Not yet recruiting | Sponsor: Ono Pharmaceutical Co. Ltd

New P3 trial • Polycythemia Vera

Sapablursen: “Met primary endpoint: Reduction in phlebotomy rate”; Polycythemia vera (Ono Pharmaceuticals, 44th Annual J.P. Morgan Healthcare Conference)

P2a data • Hematological Malignancies • Oncology • Polycythemia Vera

Sapablursen: “Met primary endpoint: Reduction in phlebotomy rate”; Polycythemia vera (Ono Pharmaceuticals, 44th Annual J.P. Morgan Healthcare Conference)

P2a data • Hematological Malignancies • Oncology • Polycythemia Vera

Deciphera Announces Oral Presentation of Positive Topline Results from Phase 2a Study of Sapablursen in Polycythemia Vera at the 67th American Society of Hematology (ASH) Annual Meeting (Businesswire) - "In both cohorts, the study achieved its primary endpoint of significantly decreasing weekly phlebotomy rate from baseline to weeks 17-37; with a decrease from 0.15 to 0.05 in Cohort A (p<0.0001) and from 0.17 to 0.07 in Cohort B (p=0.0001). In patients who completed the 37-week treatment period, the median number of phlebotomies during the last 20 weeks of treatment (weeks 17-37) decreased to 0 and 1.5 phlebotomies in Cohort A and B, respectively, compared to 5 phlebotomies in the 26 weeks (6 months) prior to treatment for both cohorts....Based on the positive Phase 2a study, Deciphera plans to initiate a Phase 3 study of sapablursen in patients with PV in 2026."

New P3 trial • P2a data • Polycythemia Vera

Sapablursen: Primary completion of P2 trial (NCT05143957) for polycythemia vera in FY2025 (Ono Pharmaceuticals) - Q2 FY2025 Results

Trial primary completion date • Hematological Malignancies • Oncology • Polycythemia Vera

Ionis reports third quarter 2025 financial results… (Businesswire) - "Revenue increased 17% in the third quarter of 2025 and increased 55% in the nine months ended September 30, 2025, compared to the same periods last year, driven by the continued successful launch of TRYNGOLZA and increased royalty revenues. Contributing to the year-to-date increase, Ionis earned a $280 million upfront payment for the global license of sapablursen to Ono Pharmaceutical Co., Ltd. in the second quarter of 2025."

Commercial • Familial Chylomicronemia Syndrome • Myeloproliferative Neoplasm • Polycythemia Vera

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

STUDY DESIGN AND DEMOGRAPHICS OF IMPRSSION, A PHASE 2 OPEN-LABEL CLINICAL TRIAL EVALUATING TMPRSS6 ANTISENSE INHIBITOR SAPABLURSEN, IN POLYCYTHEMIA VERA (EHA 2025) - P2 | "This phase 2 study is designed to assess hematocrit control, reduction in phlebotomy, safety and pharmacokinetics of sapablursen in patients with PV."

Clinical • P2 data • Cardiovascular • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Thrombosis • JAK2 • KLK7 • TMPRSS6

Ono Enters into License Agreement with Ionis Pharmaceuticals for Sapablursen for the Treatment of Polycythemia Vera (Businesswire) - "Ono Pharmaceutical...announced that it has entered into a license agreement with Ionis Pharmaceuticals...for sapablursen, an investigational RNA-targeted medicine for the treatment of polycythemia vera (PV)....Under the agreement, ONO will obtain an exclusive license to develop and commercialize sapablursen worldwide. Ionis will remain responsible for the completion of the ongoing Phase 2 IMPRSSION study, while ONO will be solely responsible for subsequent development, regulatory filings and commercialization. ONO will make an upfront payment of 280 million US dollars, with up to a maximum of 660 million US dollars in additional payments based on the achievement of development, regulatory and sales milestones. ONO will also pay to Ionis royalties in the mid-teens on annual net sales of sapablursen."

Licensing / partnership • Polycythemia Vera

A Study to Evaluate Sapablursen (Formerly ISIS 702843, IONIS-TMPRSS6-LRx) in Patients With Polycythemia Vera (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Trial primary completion date: Jan 2025 ➔ Jun 2025 | Trial completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Polycythemia Vera

A Study to Evaluate Sapablursen (Formerly ISIS 702843, IONIS-TMPRSS6-LRx) in Patients With Polycythemia Vera (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Polycythemia Vera