sovleplenib (HMPL-523) / Hutchmed - LARVOL DELTA

Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomised, double-blind, placebo-controlled, phase 3 study. (PubMed, Lancet Haematol) - P3 | "Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life. Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received one or more previous therapy."

Journal • P3 data • Cardiovascular • Hematological Disorders • Hypertension • Oncology • Thrombocytopenia • Thrombocytopenic Purpura • SYK

Comparison of different SYK-inhibitors in platelet-rich plasma (ISTH 2026) - "Methods Platelet-rich plasma (PRP) from healthy donors (n=3; technical duplicates) was incubated with SYK inhibitors (Sovleplenib, P505-15, R406, BI2494) at 100 µM-100 nM...Saracatinib (pan-Src-family kinase inhibitor) and Pirtobrutinib (BTK inhibitor) served as comparators...These findings provide a baseline reference for subsequent studies in CKD patient samples to define how CKD- associated inflammation modifies SYK-dependent platelet responses. Table or Figure Upload (1) Page 2 DOI*10.1016/j.rpth.2026.105268"

Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Inflammation • Nephrology • Renal Disease • Thrombosis • SYK

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 STUDY OF ESLIM-02 FOR EFFICACY AND SAFETY OF SOVLEPLENIB (HMPL-523) IN PATIENTS WITH WARM AUTOIMMUNE HEMOLYTIC ANEMIA IN CHINA (EHA 2026) - P2/3 | "The median prior line of anti-wAIHA treatments was both 3.0, and 36% vs 41% of pts have received rituximab. Summary/Conclusion Sovleplenib demonstrated significantly and clinically meaningful durable Hb response with a favorable safety profile. Sovleplenib could be a breakthrough therapy for pts with wAIHA who have insufficient response to previous glucocorticoid treatment."

Clinical • P3 data • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • Infectious Disease • Respiratory Diseases • SYK

SOVLEPLENIB AMELIORATES APLASTIC ANEMIA THROUGH THE MODULATION OF CGAS-STING-NF-ΚB PATHWAY (EHA 2026) - "Background Aplastic anemia (AA) is a bone marrow failure syndrome characterized by pancytopenia.Aberrantly activated T lymphocytes and their excessive secretion of cytokines, particularly interferon-gamma (IFN- γ ) and tumor necrosis factor-alpha (TNF- α ), are key drivers of this excessive hematopoietic cell apoptosis.Studies have confirmed that combining the thrombopoietin receptor agonists (TPO-RAs) eltrombopag with standard immunosuppressive therapy significantly enhances efficacy, accompanied by a significant recovery in bone marrow CD34+ cell counts and the frequency of early hematopoietic progenitor cells.However,some patients show no or insufficient response or relapse TPO-RAs may also be associated with a risk of clonal evolution, particularly the emergence of high-risk cytogenetic abnormalities.Spleen tyrosine kinase (SYK), a key mediator of immune receptor signal transduction, has garnered considerable attention due to its role in autoimmune diseases. 5..."

Aplastic Anemia • Hematological Disorders • Immune Modulation • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • CD34 • CD8 • IFNG • RELA • STING • SYK • TNFA

HUTCHMED Highlights Sovleplenib ESLIM-02 Phase III Data in Warm Antibody Autoimmune Hemolytic Anemia Presented at EHA 2026 Congress (GlobeNewswire) - "In Phase III part of the study, 90 patients were randomized 1:1 to receive either sovleplenib (n=44) or placebo (n=46) at a dose of 300 mg once daily for 24 weeks. The study met its primary endpoint, with sovleplenib demonstrating a significantly higher durable response rate during weeks 5–24 compared to placebo (66% vs 15%, p<0.0001). During the 24-week double-blind treatment period, sovleplenib demonstrated superior efficacy across several key metrics; specifically, the overall response rate-defined as hemoglobin (Hb) ≥100 g/L with an increase of ≥20 g/L from baseline without rescue therapy-was significantly increased (70% vs 22%, p<0.0001)....Median time to response was 3.1 weeks for sovleplenib versus 6.3 weeks for placebo, while the median cumulative duration of response among overall responders was 16.1 versus 6.1 weeks, respectively."

P3 data • Autoimmune Hemolytic Anemia • Immunology

ESLIM-01: Phase III Study on HMPL-523 for Treatment of ITP (clinicaltrials.gov) - P3 | N=272 | Completed | Sponsor: Hutchmed | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Sep 2025

Trial completion • Trial completion date • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

HUTCHMED Announces NDA Acceptance in China with Priority Review Status and Breakthrough Designation for Sovleplenib for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (HUTCHMED Press release) - "The NDA is supported by data from ESLIM-02, a randomized, double blind, placebo-controlled China Phase II/III study in adult patients with primary or secondary wAIHA who had relapsed or were refractory to at least one prior line of standard treatment."

Breakthrough therapy • China filing • Priority review • Anemia

Safety and efficacy of HMPL-523 (Syk inhibitor) in patients with relapsed or refractory lymphoma (AACR 2024) - P1 | "Median prior lines of therapy was 4 (range 1 - 12); 86% of CLL pts were prior BTK treated and 88% of HL pts had both a PD-1 inhibitor and Brentuximab vedotin. HMPL-523 was well tolerated at the RP2D of 700 mg QD in R/R lymphoma pts. Encouraging proof of activity was demonstrated in heavily pre-treated HL and PTCL pts. Additional studies are needed to evaluate the value of SYK-inhibitor as either monotherapy or combination in these high unmet-need population."

Clinical • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Waldenstrom Macroglobulinemia • SYK

wAIHA: HMPL-523 (Sovleplenib) in the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (clinicaltrials.gov) - P2/3 | N=110 | Active, not recruiting | Sponsor: Hutchison Medipharma Limited | Trial primary completion date: Sep 2026 ➔ Nov 2025 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial primary completion date • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Sovleplenib (HMPL-523), an investigative and highly selective oral inhibitor of Syk (The Manila Times) - "A sNDA submission to the NMPA is planned in the first half of 2026 (NCT05535933)....Resubmitted NDA for ESLIM-01 ITP with additional stability studies in February 2026, to meet NMPA stipulation of a lower impurity limit. Rolling data planned to be submitted in the second half of 2026."

China filing • Autoimmune Hemolytic Anemia • Immune Thrombocytopenic Purpura

2018-523-00US1: An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma (clinicaltrials.gov) - P1/2 | N=80 | Not yet recruiting | Sponsor: Hutchison Medipharma Limited | Trial completion date: Dec 2021 ➔ Dec 2022 | Trial primary completion date: Dec 2020 ➔ Dec 2021

Trial completion date • Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

2018-523-00US1: An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: Hutchison Medipharma Limited | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

2018-523-00US1: An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma (clinicaltrials.gov) - P1/2 | N=80 | Not yet recruiting | Sponsor: Hutchison Medipharma Limited

New P1/2 trial • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

2018-523-00US1: An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma (clinicaltrials.gov) - P1 | N=87 | Terminated | Sponsor: Hutchmed | N=140 ➔ 87 | Trial completion date: Jan 2026 ➔ Mar 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Mar 2025; Study terminated by sponsor

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

2018-523-00US1: An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma (clinicaltrials.gov) - P1 | N=140 | Active, not recruiting | Sponsor: Hutchmed | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

2018-523-00US1: An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Hutchmed | Trial completion date: Aug 2024 ➔ Jan 2026 | Trial primary completion date: Aug 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

2018-523-00US1: An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Hutchison Medipharma Limited | N=80 ➔ 140 | Trial completion date: Dec 2022 ➔ Aug 2024 | Trial primary completion date: Dec 2021 ➔ Aug 2023

Enrollment change • Trial completion date • Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

2018-523-00US1: An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Hutchison Medipharma Limited | Phase classification: P1/2 ➔ P1 | Initiation date: Apr 2019 ➔ Sep 2019

Phase classification • Trial initiation date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of Food Effect on Pharmacokinetics of HMPL-523 Acetate Tablets (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Hutchmed | Recruiting ➔ Completed

Trial completion

Pharmacokinetics and Bioequivalence Study of HMPL-523 Acetate Tablets in Humans (clinicaltrials.gov) - P1 | N=54 | Completed | Sponsor: Hutchmed | Recruiting ➔ Completed | Trial primary completion date: Feb 2026 ➔ Nov 2025

Trial completion • Trial primary completion date

Efficacy and mechanism of action of sovleplenib for aplastic anemia. (PubMed, Hematology) - "Its efficacy is mechanistically linked to the suppression of the overactivated cGAS-STING-NF-κB pathway, a key driver of inflammation in AA. Sovleplenib represents a promising targeted therapy for AA."

Journal • Anemia • Aplastic Anemia • Hematological Disorders • Immune Modulation • Immunology • Inflammation • CD4 • CD8 • IFNB1 • STING • SYK • TNFA

Study of Food Effect on Pharmacokinetics of HMPL-523 Acetate Tablets (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Hutchmed

New P1 trial

Pharmacokinetics and Bioequivalence Study of HMPL-523 Acetate Tablets in Humans (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Hutchmed

New P1 trial

HUTCHMED…announces that the Phase III registration part of the ESLIM-02 clinical trial of sovleplenib, a novel spleen tyrosine kinase ('Syk') inhibitor, in adult patients with warm antibody autoimmune hemolytic anemia ('wAIHA') in China has met its primary endpoint of durable hemoglobin (Hb) response rate within weeks 5 to 24 of treatment (GlobeNewswire) - "Full results of the ESLIM-02 study will be submitted for presentation at an upcoming scientific conference. HUTCHMED plans to submit the New Drug Application ('NDA') for sovleplenib for wAIHA to the China National Medical Products Administration (NMPA) in the first half of 2026."

China filing • P3 data: top line • Autoimmune Hemolytic Anemia

Feasibility assessment of indirect treatment comparison between off-label rituximab and novel treatments in patients with warm autoimmune hemolytic anemia (ASH 2025) - "Among the clinical trials included, five studied rituximab, in combination with prednisone, prednisolone, ibrutinib, or bortezomib. Three trials studied fostamatinib, while other studied treatments included pegcetacoplan, sovleplenib, parsaclisib, and rilzabrutinib...Future work should consider de novo sources of real-world evidence for rituximab that more closely align with registrational trial characteristics and endpoint definitions. However, aligning timing of endpoint measurements between registration trials and real-world data to match definitions remains challenging."

Clinical • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology