elritercept (KER-050) / Keros Therap, Jiangsu Hansoh Pharma, Takeda - LARVOL DELTA

HEMATOLOGICAL IMPROVEMENT AND OTHER CLINICAL BENEFITS OF ELRITERCEPT AS MONOTHERAPY AND IN COMBINATION WITH RUXOLITINIB IN PARTICIPANTS WITH MYELOFIBROSIS (MF) FROM THE ONGOING PHASE 2 RESTORE TRIAL (EHA 2025) - P2 | "Elritercept was generally well-tolerated and demonstrated potential to treat multiple aspects of MF. Observed improvements in Hgb and transfusion burden with stability or increase in platelets support potential to address cytopenias. Reductions in spleen volume and improved symptoms were also observed with elritercept, both as monotherapy and in combination with ruxolitinib."

Clinical • Combination therapy • Monotherapy • P2 data • Anemia • Hematological Disorders • Myelofibrosis • Thrombocytopenia • ACVR2A • INHBB • TGFB1

EFFICACY AND OUTCOMES OF NOVEL THERAPEUTIC AGENTS AS MONOTHERAPY OR IN COMBINATION WITH CONVENTIONAL THERAPY IN MYELODYSPLASTIC SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2025) - "Newer agents included Rigosertib (41%, n=312/770), Imetelstat (15%, n=118/770), Pembrolizumab (8%, n=65/770), Enasidenib (9%, n=67/770), and Sabatolimab (7%, n=53/770) Ivosidenib (6%, 45/770), Elritercept 2%, n=15 /770), Pevonedistat (3%, 21/770), Emavusertib (2%, 15/770), Atezolizumab (6%, 46/770), and Olutasidenib (2%, n=13/770). The most commonly used conventional agent was azacitidine (19%, n= 147/770)... This study highlights promising results with the investigational agents for MDS. However, large studies with more power are needed to strengthen our understanding of these investigational agents in MDS patients."

Combination therapy • Monotherapy • Retrospective data • Review • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia

RENEW TRIAL IN PROGRESS: A PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE ELRITERCEPT IN PARTICIPANTS WITH TRANSFUSION-DEPENDENT ANEMIA AND LOWER-RISK MYELODYSPLASTIC NEOPLASMS (EHA 2025) - P2, P3 | "The RENEW trial is expected to support the registration of elritercept for the treatment of anemia in adults with LR-MDS."

Clinical • P3 data • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR2A • INHBB • TGFB1

RKER-050, A MODIFIED ACTIVIN RECEPTOR TYPE IIA LIGAND TRAP, REGULATED OSTEOGENIC LINEAGE, COMPLEMENTING THE ERYTHROID RESPONSE AND REBALANCING THE OSTEO-HEMATOPOIETIC NICHE (EHA 2025) - P2 | "RKER-050 selectively modulated erythropoiesis and osteolineage cells simultaneously, demonstrating the potential to restore OHN balance. This dual-action mechanism can enhance cellular crosstalk between osteoblasts and hematopoietic stem and progenitor cells, potentially improving the supportive microenvironment for blood cell production and suggesting that elritercept could potentially restore equilibrium in hematological disorders by improving hematopoiesis and bone health."

Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Osteoporosis • Rheumatology • ACVR2A • TGFB1

ACTIVIN A INHIBITION IMPAIRED IN VITRO AML CELL MIGRATION AND IN VIVO BONE MARROW ENGRAFTMENT IN MICE (EHA 2025) - "Inhibition of ActA with RKER-050 reduced in vitro AML cell migration and decreased AML cell BM engraftment. The multifaceted role of ActA in disease and malignancies underscores its significance as a therapeutic target and the potential for ActA-modulating therapies to improve outcomes for patients with MDS or MF that may reduce the risk of progression to AML."

Preclinical • Acute Myelogenous Leukemia • Fibrosis • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR2A • PRKDC • TGFB1

HEMATOLOGIC IMPROVEMENT AND FATIGUE REDUCTION WITH ELRITERCEPT IN PARTICIPANTS WITH LOWER-RISK (LR) MYELODYSPLASTIC NEOPLASMS (MDS) WITH NON-TRANSFUSION DEPENDENT ANEMIA: RESULTS FROM AN ONGOING PHASE 2 TRIAL (EHA 2025) - P2 | "In this ongoing Phase 2 trial in NT participants with LR-MDS, elritercept was generally well tolerated, and robust Hgb responses were observed with maintenance or improvement of platelets and neutrophils, and dose modification occurred in some responders with no compromise in hematologic responses. Sustained decreases in ferritin and hepcidin were also observed alongside meaningful improvements in fatigue. Together, these data suggest potential for elritercept to provide durable benefits to NT participants by improving anemia, QoL, and iron homeostasis and/or inflammation."

P2 data • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • ACVR2A • INHBB • TGFB1

IMPROVEMENTS IN HEMATOLOGICAL PARAMETERS AND QUALITY OF LIFE (QOL) WITH ELRITERCEPT: RESULTS FROM AN ONGOING PHASE 2 TRIAL IN PARTICIPANTS WITH LOWER-RISK (LR) MYELODYSPLASTIC NEOPLASMS (MDS) (EHA 2025) - P2 | "These findings support the potential for elritercept to provide durable TI that is associated with clinically meaningful improvements in QoL, thus addressing important goals in treating LR-MDS. Fatigue burden (both experience and impact) was a primary driver of the observed improvements in QoL in TI responders vs non-responders. Importantly, clinically meaningful improvements in FACIT-Fatigue were observed early and continued to improve over time in participants with durable TI responses."

HEOR • P2 data • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • ACVR2A • INHBB • TGFB1

Emerging Therapeutic Approaches for Anemia in Myelofibrosis. (PubMed, Curr Hematol Malig Rep) - "The pathobiology of anemia is multifactorial, including progressive bone marrow fibrosis, decreased erythropoiesis due to high hepcidin levels leading to iron sequestration in the reticuloendothelial system, hypersplenism, erythropoiesis inhibition by myelosuppressive JAK inhibitors (ruxolitinib, fedratinib), and others...Conventional agents to manage anemia include erythropoiesis-stimulating agents, danazol, corticosteroids, and immunomodulatory agents, but responses are infrequent and lack durability...Momelotinib and pacritinib (ACVR1/JAK2 inhibitor) are the preferred JAK inhibitors for patients with cytopenias (anemia, thrombocytopenia). Luspatercept and elritercept are activin receptor ligand traps, promoting erythroid maturation and late-stage erythropoiesis...DISC-0974 is a first-in-class anti-hemojuvelin (positive hepcidin regulator) monoclonal antibody that decreased hepcidin expression, increased serum iron, and enhanced erythropoiesis in anemic patients with..."

Journal • Review • Anemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • ACVR1

Managing Myelofibrosis: Matching Advances in Treatments With Clinical Unmet Needs. (PubMed, Hematol Oncol) - "The janus kinase inhibitor (JAKi) ruxolitinib has been the mainstay of treatment for over a decade...Other JAKi (pacritinib, momelotinib, jaktinib) address treatment-related cytopenia, expanding the therapeutic utility of this class of agents to patients with baseline anemia or thrombocytopenia. Novel candidates exploit multiple molecular pathways, and offer the potential to improve the management of MF-associated cytopenia (imetelstat, pelabresib, navitoclax, selinexor, luspatercept, sotatercept, elritercept, LCL161, bomedemstat) and recover bone marrow fibrosis (imetelstat, pelabresib, navitoclax and bomedemstat). It remains to be seen if these newer agents can induce any remission in MF and enable patients to come off therapy, but the future is beginning to look much brighter."

Journal • Review • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia

Emerging Pathogenetic Mechanisms and New Drugs for Anemia in Myelofibrosis and Myelodysplastic Syndromes. (PubMed, Am J Hematol) - "These include TGF-β ligand traps (luspatercept, elritercept), activin A receptor type 1 (ACVR1)/activin receptor-like kinase 2 (ALK2) inhibitors (momelotinib, zilurgisertib), and anti-hemojuvelin antibody-based therapies (DISC-0974). Luspatercept and momelotinib are approved for anemia related to lower-risk MDS and MF, respectively, and represent an important addition to the treatment armamentarium, along with imetelstat, a telomerase inhibitor, recently ratified for anemia in lower-risk MDS. A promising strategy to overcome the limitations of existing anemia-directed therapies includes the use of drug combinations with complementary mechanisms (luspatercept + erythropoiesis stimulating agents, luspatercept + momelotinib, DISC-0974 + momelotinib), and harnessing the erythropoietic potential of sodium-glucose co-transporter-2 inhibitors (SGLT-2I). Future research should address the complex pathophysiology of anemia, standardize definitions for anemia with gender-specified..."

Journal • Review • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR1 • SMAD2 • SMAD4 • TGFB1

Keros Therapeutics Reports Recent Business Highlights and Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "In February 2025, Keros received a $200.0 million upfront payment pursuant to the exclusive license agreement it entered into with Takeda Pharmaceuticals U.S.A., Inc. (the 'Takeda Agreement') to further develop, manufacture and commercialize elritercept (KER-050) worldwide outside of mainland China, Hong Kong and Macau....Research and development expenses were $45.6 million for the fourth quarter and $173.6 million for the year ended December 31, 2024, as compared to $37.5 million for the fourth quarter and $135.3 million for the year ended December 31, 2023. The increase in research and development expenses for the fourth quarter and the year was driven by the continued advancement of the Company's pipeline, notably...the Phase 3 clinical trial of elritercept, as well as an increase in personnel costs and infrastructure to support operations and expansion of the Company's pipeline."

Commercial • Hematological Malignancies • Myelodysplastic Syndrome

Takeda Delivers Strong Third-Quarter FY2024 Results; Raises Full Year Outlook, Forecasting Revenue and Core Operating Profit Margin Growth (Businesswire) - "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 programs and indications: oveporexton (TAK-861) for the treatment of narcolepsy type 1; zasocitinib for the treatment of psoriasis...Moreover, five additional indication filings for late-stage programs are on pace for FY2027-FY2029. zasocitinib for the treatment of psoriatic arthritis; mezagitamab for treatments of immune thrombocytopenia (ITP), a rare immune-mediated bleeding disorder, and immunoglobulin A nephropathy (IgAN), a chronic progressive autoimmune mediated kidney disease; fazirsiran for the treatment of alpha-1 antitrypsin deficiency-associated liver disease, and elritercept for the treatment of anemia associated with myelodysplastic syndrome."

Filing • P3 data • Alpha-1 Antitrypsin Deficiency • Anemia • IgA Nephropathy • Immune Thrombocytopenic Purpura • Narcolepsy • Psoriasis • Psoriatic Arthritis

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

RESTORE: Study to Evaluate KER-050 as a Monotherapy or in Combination With Ruxolitinib in Myelofibrosis (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Keros Therapeutics, Inc. | Trial completion date: Jun 2025 ➔ Jan 2029 | Trial primary completion date: Apr 2025 ➔ Dec 2026

Monotherapy • Trial completion date • Trial primary completion date • Myelofibrosis

Keros Therapeutics Announces Effectiveness of Global License Agreement with Takeda to Advance Elritercept (GlobeNewswire) - "Keros Therapeutics, Inc...today announced that the global development and commercialization license agreement with Takeda...to advance elritercept became effective on January 16, 2025. The agreement, which was previously announced on December 3, 2024, became effective upon the expiration or termination of the applicable waiting period under the Hart-Scott Rodino Antitrust Improvements Act of 1976, as amended. In connection with the effectiveness of the agreement, Takeda will make an upfront payment to the Company of $200.0 million."

Licensing / partnership • Oncology

The Efficacy and Safety of Elritercept in Adult Participants with Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) with Anemia (RENEW) (clinicaltrials.gov) - P3 | N=225 | Recruiting | Sponsor: Keros Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Trial primary completion date: Mar 2032 ➔ Mar 2028

Enrollment open • Trial primary completion date • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Elritercept for Transfusion-Dependent Anemia in Lower-Risk MDS: A Trial in Progress (Blood Cancers Today) - "Rami S. Komrokji...presented the design of a phase 3 trial in progress, which is underway to evaluate the efficacy and safety of elritercept, a novel activin receptor type IIA ligand trap, to treat transfusion-dependent anemia in patients with lower-risk myelodysplastic syndromes (LR-MDS)...The global multicenter RENEW trial is a double-blind, placebo-controlled study enrolling adults with very low-, low-, or intermediate-risk MDS per the Revised International Prognostic Scoring System (IPSS-R)...The study plans to enroll 225 patients across 127 sites in 24 countries worldwide...The results of the RENEW trial are expected to support the registration of elritercept for anemia in LR-MDS."

Trial status • Anemia • Myelodysplastic Syndrome

Hematological Improvement and Other Clinical Benefits of Elritercept As Monotherapy and in Combination with Ruxolitinib in Participants with Myelofibrosis from the Ongoing Phase 2 Restore Trial (ASH 2024) - P2 | "Data also support potential for elritercept to reduce spleen size and improve TSS as monotherapy and in combination with ruxolitinib. Updated results with additional patients and longer-term data will be presented."

Clinical • Combination therapy • Monotherapy • P2 data • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Oncology • Pain • Pruritus • Thrombocytopenia • ACVR2A • INHBB • TGFB1

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

Hematologic Improvement and Fatigue Reduction with Elritercept in Participants with Lower-Risk MDS with Non-Transfusion Dependent Anemia: New Analyses from an Ongoing Phase 2 Trial (GlobeNewswire) - P2 | N=110 | RESTORE (NCT05037760) | Sponsor: Keros Therapeutics, Inc. | "In a subgroup analysis of patients that were non-transfused ('NT') at baseline, treatment with elritercept showed: Robust hematological responses observed with 93.3% (n=14/15) of NT patients having an increase greater than 1.0 g/dL and 86.7% (n=13/15) having an HI-E response; Durable HI-E responses observed with elritercept treatment with 100% (n=13/13) achieving a continuous response duration of greater than 24 weeks and 76.9% (n=10/13) achieving a cumulative response duration greater than 52 weeks....Elritercept was generally well-tolerated by the safety population. There were six cases of fatal TEAEs in the trial that were each deemed unrelated to treatment."

P2 data • Myelodysplastic Syndrome

Improvements in Hematological Parameters and Quality of Life (’QoL’) with Elritercept: Results from an Ongoing Phase 2 Trial in Participants with Lower-Risk MDS (GlobeNewswire) - P2 | N=140 | NCT04419649 | Sponsor: Keros Therapeutics, Inc | "Elritercept was generally well-tolerated in the safety population....Elritercept was generally well-tolerated in the safety population. Of the patients with HTB, 31.4% (n=16/51) achieved TI for at least eight weeks during the first 24 weeks of treatment. Eight of those 16 patients (50.0%) achieved TI for at least 24 weeks over the first 48 weeks of treatment....The FACIT-Fatigue scale...was utilized to assess health-related quality of life, including in a subgroup of patients (n=17) achieving TI for at least 24 weeks over the first 48 weeks of treatment. Patients in this subgroup showed clinically meaningful improvements in QoL, and meaningful improvements in FACIT-Fatigue were observed early and generally continued to improve over time in patients with more durable TI responses."

P2 data • Myelodysplastic Syndrome • Oncology

Elritercept: Regulatory submission for MDS in FY2027/FY2029 (Takeda) - R&D Day

Filing • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Activin a Inhibition Impaired Human AML Cell Engraftment and Extended Survival in Immunodeficient Mice (ASH 2024) - "Taken together, RKER-050 reduced AML cell bone marrow engraftment and improved survival of AML cell-burdened mice.Conclusions : Inhibition of ActA with RKER-050 reduced in vitro AML cell migration and decreased AML cell bone marrow engraftment, leading to extended survival in mice. The multifaceted role of ActA in disease and malignancies underscores its significance as a therapeutic target and the potential for ActA-modulating therapies to improve outcomes for patients with MDS or MF by reducing the risk of progression to AML."

Preclinical • Acute Myelogenous Leukemia • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Metabolic Disorders • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR2A • CXCL12 • PRKDC • TGFB1

Renew Trial in Progress: A Phase 3, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Elritercept (KER-050) for the Treatment of Transfusion-Dependent Anemia in Adult Participants with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Neoplasms (MDS) (ASH 2024) - P2, P3 | "Secondary endpoints are the proportion of participants with achievement of TI ≥24 weeks from baseline through week 48, the proportion of participants with HTB achieving TI for ≥8 weeks from baseline through week 24, and the incidence and severity of adverse events (AEs) and serious AEs. The RENEW trial is expected to support the registration of elritercept for the treatment of anemia in adults with LR-MDS."

Clinical • P3 data • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR2A • INHBB • TGFB1

Hematologic Improvement and Fatigue Reduction with Elritercept (KER-050) in Participants with Lower-Risk (LR) Myelodysplastic Neoplasms (MDS) with Non-Transfusion Dependent Anemia: New Analyses from an Ongoing Phase 2 Trial (ASH 2024) - P2 | "Clinically meaningful improvements in fatigue, as well as rapid and sustained decreases in ferritin and hepcidin, were observed. Together, these data suggest potential for elritercept to provide durable and sustained benefits to NT participants with LR-MDS by improving anemia, QoL, and iron homeostasis and/or inflammation."

P2 data • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology • ACVR2A • INHBB • TGFB1