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

Hematological and clinical improvements with elritercept (KER-050, TAK-226) at the recommended Phase 2 dose (RP2D) in patients with myelofibrosis (MF) receiving ruxolitinib: Updated results from the Phase 2 restore trial (ASH 2025) - P2 | "For the remainder of pts with available data, the VAFremained unchanged at wks 24 and 52 with further follow-up ongoing.ConclusionsElritercept as an add on treatment at the RP2D demonstrated clinically meaningful improvements inanemia, thrombocytopenia, spleen volume and symptoms in MF pts receiving ruxolitinib. Emerging datasuggest potential effects on clonal architecture and hematopoietic restoration, even in advanced disease.These findings support elritercept as a differentiated therapy in the treatment of pts with MF."

Clinical • P2 data • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytopenia • ACVR2A • INHBB • JAK2 • TGFB1

Elritercept shows durable responses in lower-risk myelodysplastic neoplasms (LR-MDS) with transfusion dependence: Updated Results from an ongoing Phase 2 trial (ASH 2025) - P2, P3 | "As of April 3, 2025, 78 pts treated with elritercept starting at the recommended Part 2 dose(RP2D; 3.75 mg/kg) were evaluable for the mITT24 analysis of TI and the median exposure was 11.9months. In the first 24 weeks of treatment, 38.5% of pts achieved TI ≥8 weeks. In the first 48 weeks, 26.9%achieved TI ≥24 weeks (15.5% in patients with HTB) with 75.9% maintaining TI at 48 weeks."

P2 data • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • ACVR2A • HEY1 • SF3B1 • TGFB1

Optimizing elritercept benefit-risk profile by response-based adaptive dosing in patients with low-risk Myelodysplastic Syndromes (LR-MDS) (ASH 2025) - "The integrated analysis supports response-based adaptive dosing of elritercept in LR-MDSpatients with a starting dose of 3.75 mg/kg Q4W."

Clinical • Hematological Disorders • Hematological Malignancies • Hepatology • Myelodysplastic Syndrome • Renal Disease • ACVR2A • INHBB • TGFB1

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 • Pruritus • Thrombocytopenia • ACVR2A • INHBB • TGFB1

Modulation of TGF-β Superfamily Signaling By Ker-050 Demonstrated Potential to Treat Myelofibrosis and Mitigate Ruxolitinib-Associated Cytopenia (ASH 2023) - P2 | "A total of 24 participants were enrolled (n=12 in Arm 1A and n=12 in 1B). One participant recently enrolled in Arm 1B at dose level III (3.0 mg/kg) had limited exposure at the time of data cutoff and is not included in the PD findings reported below. All participants met the criteria for higher-risk disease by DIPSS and 41.7% met IWG 2013 transfusion-dependent (TD) criteria (Table 1)."

Anemia • Fatigue • Fibrosis • Gastrointestinal Disorder • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis • ACVR2A • TGFB1

Rker-050, a Modified Activin Receptor Type Iia Ligand Trap, Promoted Erythropoiesis in a Murine Model of Myelofibrosis (ASH 2023) - "Reestablishing BM hematopoiesis could obviate the need for compensatory extramedullary hematopoiesis in the spleen, the major driver of splenomegaly in MF patients. In conclusion, KER-050 represents a potentially promising approach for patients with MF and other hematological diseases where ineffective hematopoiesis occurs."

Preclinical • Anemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • ACVR2A • GATA1 • INHBB • TGFB1

Ker-050 Treatment Reduced Iron Overload and Increased Bone Specific Alkaline Phosphatase in Participants with Lower-Risk MDS Supporting Potential to Restore Balance to the Osteohematopoietic Niche (ASH 2023) - P2 | "Baseline ferritin levels in RP2D participants (N=59) were generally elevated, while levels of mean corpuscular hemoglobin and reticulocyte hemoglobin were in the normal range (Table 1). After KER-050 treatment, sustained decreases in serum ferritin were observed among participants with baseline levels ≥1000 ng/mL (Figure 1), likely driven in part by reduced transfusion burden in responders. Concomitant increases observed in soluble transferrin receptor (sTfR; Figure 1) suggest that increased erythropoiesis may also have contributed."

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

Durable Clinical Benefit with Ker-050 Treatment: Findings from an Ongoing Phase 2 Study in Participants with Lower-Risk MDS (ASH 2023) - P2 | "At baseline, most participants receiving KER-050 at the RP2D (74.6%) required regular transfusions (≥2 RBC units/8 weeks); 52.5% of RP2D participants had HTB (≥4 RBC units/8 weeks) and 20.3% had ≥8 RBC units/8 weeks (Table 1). The median treatment duration was 166 days (range 6 to 649). Most participants (89.8%) had at least 1 treatment-emergent adverse event (TEAE), and 32.2% had TEAEs considered treatment-related (Table 1)."

Clinical • P2 data • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Myelodysplastic Syndrome • Myelofibrosis • Novel Coronavirus Disease • Oncology • Pulmonary Disease • ACVR2A • TGFB1

Rker-050, a Modified Activin Receptor Type Iia Ligand Trap, Regulates Osteogenic Lineage, Complementing the Erythroid Response and Rebalancing the Osteo-Hematopoietic Niche (ASH 2024) - P2 | "This dual-action mechanism can enhance critical cellular crosstalk between osteoblasts and hematopoietic stem and progenitor cells, potentially improving the supportive microenvironment for blood cell production. This selective mechanism suggests that elritercept could potentially restore equilibrium in patients with hematological disorders by improving hematopoiesis and promoting bone anabolism."

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

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 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

Improvements in Hematological Parameters and Quality of Life (QOL) with Elritercept (KER-050): Results from an Ongoing Phase 2 Trial in Participants with Lower-Risk (LR) Myelodysplastic Neoplasms (MDS) (ASH 2024) - P2 | "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 fatigue scores were observed early and continued to improve over time in participants with more durable TI responses."

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

KER050-MD-201: A Study of Elritercept to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Takeda | Trial completion date: Oct 2030 ➔ Oct 2031

Trial completion date • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

RESTORE: A Study of Elritercept Alone or Together With Ruxolitinib in Adults With Myelofibrosis (clinicaltrials.gov) - P2 | N=135 | Recruiting | Sponsor: Takeda | Trial completion date: Jan 2029 ➔ Feb 2030 | Trial primary completion date: Dec 2026 ➔ Feb 2028

Monotherapy • Trial completion date • Trial primary completion date • Anemia • Hematological Disorders • Myelofibrosis

KER-050: Initiation of P3 trial for 1L-anemia associated MDS between FY 2025-FY 2026 (Takeda) - Q2 FY2025 Results: Proof-of-concept data readout from P2 trial (NCT05037760) for anemia associated myelofibrosis in FY 2025-FY 2026

New P3 trial • P2 data • Myelodysplastic Syndrome • Myelofibrosis • Oncology

Individualizing Treatment Selection in MF (SOHO 2025) - P3 | "These include the activin receptor ligand trap luspatercept, the telomerase inhibitor imetelstat, the selective inhibitor of nuclear export selinexor, the human double minute 2 inhibitor navtemadlin, and the bromodomain and extra-terminal protein inhibitor pelabresib...Elritercept — another activin receptor ligand trap — and the anti-hemojuvelin antibody DISC-0974 are being developed for anemia of MF...Currently, these patients are observed or managed for thrombotic risk similarly to those with essential thrombocythemia (ET) — receiving hydroxyurea for control of cytoses, ruxolitinib for symptoms, or interferon for long-term disease modification. Encouraging data on ruxolitinib in patients with intermediate-1-risk MF, along with analyses from the COMFORT trials demonstrating the benefits of early initiation of ruxolitinib in patients with intermediate-2/high-risk MF and intriguing evidence of event-free survival (EFS) improvement with both ruxolitinib and..."

Clinical • Essential Thrombocythemia • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Non-melanoma Skin Cancer • Oncology • Polycythemia Vera • Skin Cancer • Solid Tumor • ACVR1 • IRAK1

KER050-MD-201: A Study of KER-050 to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (clinicaltrials.gov) - P2 | N=140 | Recruiting | Sponsor: Takeda | Trial completion date: Nov 2025 ➔ Oct 2030 | Trial primary completion date: Jun 2025 ➔ Oct 2029

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

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 (SOHO 2025) - P2, P3 | "The primary endpoint is the proportion of participants achieving transfusion independence (TI) ≥8 weeks from baseline through week 24. The secondary endpoints are the proportion of participants achieving TI ≥24 weeks from baseline through week 48, the proportion with HTB achieving TI for ≥8 weeks from baseline through week 24, and the incidence and severity of adverse events and serious adverse events."

Clinical • P3 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Oncology

Pharmacokinetic/Pharmacodynamic Analysis of Elritercept in Phase 2 Studies Shows Efficacy in Anemia Treatment for Lower-Risk Myelodysplastic Neoplasms and Myelofibrosis (SOHO 2025) - P2 | "Elritercept demonstrated dose-dependent improvements in anemia-related outcomes in patients with LR-MDS and MF, with higher doses correlating with enhanced efficacy. Dosing of 3.75 mg/kg Q4W, with optional titration to 5.0 mg/kg, is recommended for further evaluation in LR-MDS and MF."

Clinical • P2 data • PK/PD data • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR2A • TGFB1

Elritercept: Regulatory filing for 2L Anemia-associated MDS in FY2027-FY2029 (Takeda) - Q1 FY2025 Results

Filing • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Keros Therapeutics Announces the First Patient Dosing in the Phase 3 RENEW Clinical Trial of Elritercept (GlobeNewswire) - "Keros Therapeutics,,,announced that the first patient was dosed in the Phase 3 RENEW clinical trial of elritercept in adults with transfusion-dependent anemia with very low, low, or intermediate risk myelodysplastic syndromes ('MDS'). The dosing of the first patient triggers a $10 million milestone payment to Keros under the global license agreement with Takeda....The elritercept Phase 3 RENEW clinical trial (NCT06499285) is a global, randomized, double-blind, placebo-controlled trial in adults with transfusion-dependent anemia with very low, low, and intermediate risk MDS. The primary objective is to evaluate the efficacy of elritercept in reducing red blood cell transfusions."

Financing • Trial status • Anemia • Myelodysplastic Syndrome

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