flonoltinib / Baoling Bio - LARVOL DELTA

Preliminary analysis of a phase 2b, randomized, active-control study of flonoltinib maleate (FM) vs. ruxolitinib in intermediate-2 or high-risk myelofibrosis patients (ASH 2025) - P1/2, P2 | "The updated results for the phase 2b of 75 MFpatients will be completed in December 2025. A pivotal phase III multicenter, randomized, positivecontrol, double blind clinical trial in China is currently in discussion with regulatory authority."

Clinical • P2b data • Fibrosis • Immunology • Myelofibrosis • Thrombocytopenia • CALR • CDK6 • FLT3 • TGFB1

Phase IIa Study on Flonoltinib Maleate Tablets in the Treatment of Patients With Polycythemia Vera (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd

New P2 trial • Tumor mutational burden • Polycythemia Vera

First-in-Human Phase I/IIa Safety and Efficacy of Flonoltinib Maleate, a New Generation of JAK2/FLT3 Inhibitor in Myelofibrosis (ASH 2024) - P1/2 | "FM may be a new treatment option for myelofibrosis pts. A randomized, open-label, positive-controlled, multicenter Phase II trial is currently underway in patients with moderate-risk myelofibrosis treated with FM."

Clinical • First-in-human • P1/2 data • Anemia • Cardiovascular • Fibrosis • Hypertension • Immunology • Infectious Disease • Leukopenia • Myelofibrosis • Myeloproliferative Neoplasm • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia • Thrombocytosis • JAK1 • JAK2 • JAK3

Safety of Flonoltinib Maleate Tablets for the Treatment of Patients With Myeloproliferative (clinicaltrials.gov) - P1/2 | N=31 | Completed | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ Mar 2025

Trial completion • Trial completion date • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

A Pharmacokinetic Study of the Food Effect on Flonoltinib Maleate Tablets (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd

New P1 trial

A Phase I Clinical Study of Flonoltinib Maleate Tablets in Healthy Subjects (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Recruiting ➔ Completed

Trial completion

Another innovative drug of Zeling Biopharma has obtained FDA clinical trial approval, accelerating its global layout [Google translation] (bydrug.pharmcube.com) - "Recently, the innovative Class 1 chemical drug Flonoltinib Maleate Tablets (hereinafter referred to as 'Flonoltinib') developed by Chengdu Zeling Biopharmaceutical Technology Co., Ltd. (hereinafter referred to as 'Zeling Bio') has obtained the clinical trial approval (IND) from the U.S. Food and Drug Administration (FDA), and has been approved to conduct Phase I/II clinical trials for the treatment of myeloproliferative neoplasms (MPN) in the United States."

IND • New P1/2 trial • Myeloproliferative Neoplasm

Flonoltinib Maleate Provides Durable Spleen Reduction and Symptom Improvement in Myelofibrosis (OncLive) - P1/2a | N=31 | NCT05153343 | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | "Flonoltinib maleate generated rapid clinical benefits, including spleen volume reduction and symptom improvement, for patients with myelofibrosis....As of the data cutoff of September 5, 2024, 77.3% of evaluable patients (n = 22) in the overall study population (n = 30) achieved at least a 35% reduction in spleen volume (SVR35) from baseline at 24 weeks. Two patients achieved SVR35 during cycles 22 and 24, respectively. The best spleen response rate in the overall population was 86.7%, and 76.7% of patients experienced at least a 50% reduction in total symptom burden (TSS50). Bone marrow fibrosis improvement was also observed in 26.1% of patients."

P1/2 data • Myelofibrosis

Flunotinib Maleate Phase II Intermediate-High Risk Bone Fiber Clinical Trial (clinicaltrials.gov) - P2 | N=75 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd

New P2 trial • Myelofibrosis

Study on tissue distribution, metabolite profiling, and excretion of [C]-labeled flonoltinib maleate in rats. (PubMed, J Pharm Biomed Anal) - "A minor fraction of FM (<10 %) was excreted through renal excretion in the form of urine. Integration of the current results with previous pharmacokinetic investigations of FM in rats and dogs enables a comprehensive elucidation of the in vivo ADME processes and characteristics of FM, thereby establishing a solid foundation for subsequent clinical investigations of FM."

Journal • Preclinical • Metabolic Disorders • Myeloproliferative Neoplasm • Oncology • FLT3 • JAK2

Novel janus-kinase (JAK) inhibitors in myelofibrosis. (PubMed, Expert Opin Investig Drugs) - "This review includes the current status of JAKi treatment for myelofibrosis, mainly focusing on investigational JAKis; jaktinib, lestaurtinib, itacitinib, gandotinib, BMS-911543, ilginatinib, TQ05105, and flonoltinib maleate...In patients with myelofibrosis, momelotinib was effective in treating anemia, whereas jaktinib was effective in both anemia and Total Symptom Score (TSS)...The increasing variety of JAKis will allow for more personalized treatment options for myelofibrosis in the future. The potential impact on disease progression, molecular responses, and the duration of this response will become important parameters for future evaluations of these drugs."

Journal • Review • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Safety of Flunotinib Maleate Tablets for the Treatment of Patients With Myeloproliferative (clinicaltrials.gov) - P1/2 | N=31 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Phase classification: P1 ➔ P1/2

Phase classification • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection (clinicaltrials.gov) - P=N/A | N=66 | Active, not recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2023 ➔ Nov 2023 | Trial primary completion date: Jun 2023 ➔ Nov 2023

Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • IL6

UPLC-MS/MS method development and application to pharmacokinetic study in rats and dogs of Flonoltinib Maleat. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "When the sample concentration was higher than the upper limit of quantitation (ULOQ), the 10-fold dilution was reliable within the limits of acceptability. The UPLC-MS/MS method developed in this study was successfully applied in measuring the pharmacokinetic parameters of FM in rats and dogs after intravenous and oral administration, laying a foundation for the preclinical pharmacokinetic study of FM and providing a reference for clinical pharmacokinetic studies."

Journal • PK/PD data • Preclinical • Myeloproliferative Neoplasm • Oncology • FLT3

Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection (clinicaltrials.gov) - P=N/A | N=66 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd

New trial • Infectious Disease • Novel Coronavirus Disease • Solid Tumor • IL6

Study of Flonoltinib Maleate Tablets in the Treatment of Proliferative Bone Marrow Tumors (clinicaltrials.gov) - P1 | N=31 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Trial completion date: Feb 2023 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Nov 2023

Trial completion date • Trial primary completion date • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Flonoltinib, a Novel JAK2/FLT3 Inhibitor, Potently Treats Hemophagocytic Lymphohistiocytosis and Increases Sensitivity to Dexamethasone (ASH 2022) - "Subsequently, secondary HLH murine model was established by intraperitoneal injection of 50 μg CpG-ODN1826 to C57BL/6 mice...Flonoltinib plus dexamethasone also exerted stronger effect in reducing spleen weight and elevating CBC than etoposide plus dexamethasone...Conclusions Compared to ruxolitinib, the novel JAK2/FLT3 inhibitor, flonoltinib, was more effective in treating HLH. Flonoltinib was synergistic with dexamethasone by restoring GCR nuclear transport, which increased sensitivity to dexamethasone."

Hematological Disorders • Immunology • Myeloproliferative Neoplasm • Oncology • Rare Diseases • CD8 • FLT3 • IL6 • JAK2 • PRF1 • STAT1 • STAT3 • STAT5 • TNFA

Study of Flonoltinib Maleate Tablets in the Treatment of Proliferative Bone Marrow Tumors (clinicaltrials.gov) - P1 | N=31 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Myelofibrosis • Myeloproliferative Neoplasm • Oncology

Preclinical studies of Flonoltinib Maleate, a novel JAK2/FLT3 inhibitor, in treatment of JAK2-induced myeloproliferative neoplasms. (PubMed, Blood Cancer J) - "Long-term FM treatment showed good pharmacokinetic/pharmacodynamic characteristics with high drug exposure in tumor-bearing tissues and low toxicity. Currently, FM has been approved by the National Medical Products Administration of China (CXHL2000628), and this study will guide clinical trials for patients with MPNs."

Journal • Preclinical • Bone Marrow Transplantation • Fibrosis • Immunology • Myeloproliferative Neoplasm • Oncology • Transplantation • FLT3