tasquinimod (ABR-215050) / Active Biotech - LARVOL DELTA

Preclinical Studies Demonstrating Efficacy of Tasquinimod in Models of Advanced Myeloproliferative Neoplasm (MPN) in Blastic Phase (ASH 2023) - "Additionally, our findings showed that co-treatment with TM (5 to 30 µM) and ruxolitinib (250 to 1000 nM), BET inhibitor OTX015 (50 to 250 nM) or pelabresib (CPI-0610) (100 to 500 nM), or BCL2/Bcl-xL inhibitor navitoclax induced synergistic lethality in advanced MPN-BP cells exhibiting delta synergy scores of >1.0 (by the ZIP method). In a separate experiment on the same PDX model, treatment with TM (30 mg/kg/day) also induced significantly greater survival advantage than treatment with ruxolitinib (30 mg/kg/day) or OTX015 (30 mg/kg/day) by oral gavage. These findings clearly demonstrate preclinical efficacy of TM in advanced MPN-BP cellular models and create the rationale to further interrogate the efficacy of TM alone and in combinations with current, front-line therapies for advanced MPN with excess blasts."

IO biomarker • Metastases • Preclinical • Fibrosis • Immunology • Inflammation • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • BCL2 • BCL2L1 • CALR • CCND1 • CD123 • CD33 • CD34 • CD99 • CDK6 • CDKN1A • CLEC12A • CXCR4 • IL3RA • IL6 • ITGAM • JAK2 • MPO • MYC • NLRP3 • S100A8 • S100A9 • TERT • TLR4 • TNFA

Evaluation of the Lethal Activity and Its Mechanism of Tasquinimod in Advanced Myeloproliferative Neoplasm (MPN) in Blastic Phase (ASH 2024) - "Importantly, cotreatment with TQ (5 to 30 µM) and ruxolitinib (250 to 1000 nM), BET inhibitor OTX015 (50 to 250 nM) or pelabresib (CPI-0610) (100 to 500 nM), or BCL2/Bcl-xL inhibitor navitoclax, induced synergistic lethality in advanced MPN-BP cells, represented by delta synergy scores of >1.0 (by the ZIP method)...Co-treatment with TQ and RGFP966 (HDAC3i) induced synergistic lethality in post-MPN sAML cells...These findings demonstrate the pre-clinical efficacy of TQ and/or JAKi or BETi or with novel agents identified here in advanced MPN and MPN-AML cells. They also create the rationale to further interrogate the pre-clinical efficacy of the TQ-based combinations against cellular models of advanced MPN."

IO biomarker • Metastases • Fibrosis • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • BCL2 • BCL2L1 • CALR • CCL2 • CCND1 • CD123 • CD33 • CD34 • CD99 • CDK6 • CDKN1A • CLEC12A • CXCL12 • CXCL8 • CXCR4 • HDAC3 • IL1A • IL3RA • IL6 • ITGAM • JAK2 • MPO • MYC • NLRP3 • NSD2 • S100A8 • S100A9 • TERT • TLR4 • TNFA • TP53

Active Biotech expands US collaboration to advance tasquinimod clinical development in myelofibrosis (Active Biotech Press Release) - "The collaboration involves a preclinical research program aimed at further detailing and validating the therapeutic potential of tasquinimod in myelofibrosis, while laying the foundation for expanding the ongoing clinical program for tasquinimod in US through a partnership with MPN-RC, a network of leading research investigators at major US institutions dedicated to developing improved treatments for myeloproliferative neoplasms. In addition to Mount Sinai Health System, New York, the MPN-RC includes sites such as Memorial Sloan Kettering Cancer Center, New York, Moffit Cancer Center, Tampa, Atrium Health Wake Forest, Winston Salem and Yale School of Medicine, New Haven....The primary objective of the preclinical program is to evaluate the anti-tumor activity of tasquinimod both as a monotherapy and in combination with selected treatments of strategic interest."

Licensing / partnership • Myelofibrosis

Active Biotech…announced that the first patient has been dosed in the Phase Ib/II clinical study of tasquinimod following an amendment to the study protocol, with increased flexibility in the dosing regimen of tasquinimod. (Active Biotech Press Release)

Trial status • Myelofibrosis

Neutrophil-derived S100A8/A9 impairs megakaryocyte maturation in immune thrombocytopenia. (PubMed, Nat Commun) - "In primary CD34+-derived megakaryocyte cultures, ITP plasma reduces polyploidization, maturation-marker expression, and platelet-like particle release; tasquinimod treatment or TLR4 inhibition partially restores these endpoints...Together, these complementary data position neutrophils as contributors to thrombopoietic failure in ITP, connect marrow inflammation to defective platelet production, and nominate the S100A8/A9-TLR4-JNK/c-Jun axis as a therapeutic target. Modulating this pathway partially restores megakaryopoiesis and alleviates thrombocytopenia in vivo, supporting pharmacologic targeting of S100A8/A9-TLR4 signaling as a potential adjunct to ITP therapy."

Journal • Hematological Disorders • Immune Thrombocytopenic Purpura • Inflammation • Thrombocytopenia • Thrombocytopenic Purpura • CD34 • GATA1 • S100A8

HDAC4 regulates hASC osteogenesis and bone regeneration by mediating SMAD4 via histone acetylation. (PubMed, Stem Cell Reports) - "A sustained-release hydrogel delivering tasquinimod was developed and demonstrated to significantly enhance bone regeneration in critical-sized cranial and mandibular defects in mice. The findings reveal a promising localized epigenetic strategy for repairing craniofacial bone defects."

Journal • HDAC4 • SMAD4

An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer. (PubMed, Nat Commun) - "TP1 exhibits stronger radiosensitizing effects than tasquinimod in lung cancer organoids and xenograft models. Our findings uncover HDAC4 as a suppressor of ferroptosis in radioresistance and present a PROTAC-based strategy to enhance radiotherapy efficacy."

Journal • Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CYP1A1 • HDAC4 • TP53

European regulatory approval obtained to resume enrolment in the HOVON 172 MF study evaluating tasquinimod in myelofibrosis and conducted in collaboration between Active Biotech, Oncode and HOVON. (TradingView) - "Active Biotech announced positive feedback from the European regulatory authorities and ethics committee regarding the clinical proof-of-concept study of tasquinimod in myelofibrosis (HOVON 172 MF, NCT06605586). The study is conducted within the HOVON network of leading clinics in the Netherlands and Germany is now cleared to resume patient recruitment...A protocol amendment was submitted to the authorities and ethics committee, with the aim to increase the flexibility in the dosing regimen of tasquinimod...With the amendment now approved, the study is well positioned to move forward, and recruitment will resume shortly."

Enrollment status • Myelofibrosis

IgG2a-formatted 4-1BB agonism combined with S100A9 inhibition enhances T cell activation and tumor control in a preclinical model of multiple myeloma. (PubMed, J Exp Clin Cancer Res) - "These findings establish the isotype-specific efficacy of 4-1BB agonists and support 4-1BB stimulation combined with TQ as a promising strategy to enhance durable immunotherapeutic responses in MM."

IO biomarker • Journal • Preclinical • Hematological Malignancies • Immune Modulation • Immunology • Multiple Myeloma • Oncology • CD86 • GZMB • IFNG • NCAM1 • S100A9 • TNFRSF9

HOVON 172 MF: Tasquinimod in Patients with Myelofibrosis Refractory to or Intolerant for JAK2 Inhibition (clinicaltrials.gov) - P1/2 | N=26 | Active, not recruiting | Sponsor: Stichting Hemato-Oncologie voor Volwassenen Nederland | Recruiting ➔ Active, not recruiting | N=20 ➔ 26 | Active, not recruiting ➔ Recruiting

Enrollment change • Enrollment closed • Enrollment open • Myelofibrosis

Preclinical efficacy of tasquinimod in myelodysplastic neoplasms: Restoring erythropoiesis and mitigating bone loss. (PubMed, Hemasphere) - "Our findings suggest that TASQ mitigates inflammasome activation in the MDS BM, improving erythropoiesis and bone health. These results provide a necessary preclinical basis for clinical trials in lower risk MDS patients, in whom anemia and osteoporosis often coexist."

IO biomarker • Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Osteoporosis • Rheumatology • IL18 • IL1B • IRAK1 • PD-L1 • S100A9 • TLR4

Discovery of 1,2-dihydro-4-hydroxy-2-oxoquinoline-3-carboxamide derivatives as potent anticancer agents: Structure-based design, synthesis, mechanistic insights, target identification, and molecular docking studies. (PubMed, Bioorg Chem) - "The present investigation describes the design and synthesis of twenty-eight novel 1,2-dihydro-4-hydroxy-2-oxoquinoline-3-carboxamide derivatives based on Tasquinimod as the lead scaffold...Moreover, molecular docking analysis of the hub targets revealed favourable binding interactions with key cancer-related proteins, suggesting their potential inhibitory activity and supporting their predicted anticancer role. Collectively, these findings suggest that the compounds represent promising lead candidates for subsequent in vivo evaluation and potential development as novel anticancer agents."

Journal • Breast Cancer • Oncology

Open Label Phase 1/2 Study of Tasquinimod in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF) (clinicaltrials.gov) - P1/2 | N=33 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Myelofibrosis • Neutropenia • Thrombocytosis

Neutrophil S100a9 Deficiency Protects against Periodontal Bone Loss. (PubMed, J Dent Res) - "This effect was reversible in S100a9 deficiency mice upon rapamycin-induced autophagy restoration. Therapeutic intervention with the S100A9-specific inhibitor tasquinimod effectively inhibited osteoclastic differentiation of macrophages and mitigated bone loss. In conclusion, our findings reveal the mechanism by which S100A9 regulates osteoclast differentiation via NETosis, providing insights into osteoimmunological regulation in the pathogenesis of periodontitis."

Journal • Dental Disorders • Immunology • Inflammation • Osteoporosis • Periodontitis • S100A8 • S100A9

Spatially Resolved Transcriptomics Identifies Tumor-Stroma-Immune Networks and Therapeutic Targets in Endocrine-Resistant Advanced Breast Cancer Treated with Everolimus+Letrozole: Insights from the MIRACLE Trial. (PubMed, Cancer Lett) - P2 | "This finding suggests that tasquinimod, an S100A9 inhibitor, could be a viable therapeutic option. Furthermore, the interaction between MMP11 and COL16A1 in stroma-rich regions suggests that cancer-associated fibroblasts may contribute to improved outcomes. Our study underscores the critical role of spatial gene expression analysis in elucidating the tumor microenvironment and its impact on prognosis in patients undergoing E+L treatment, thereby opening new avenues for targeted interventions."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • FKBP5 • HER-2 • MMP11 • S100A9 • SERPINA1

Targeted inhibition of M2 macrophages polarization via a PDC attenuates chronic pancreatitis through the PPARα pathway. (PubMed, iScience) - "A peptide-drug conjugate (PDC) was developed for this investigation by linking the S100A9 inhibitor Tasquinimod to a peptide that selectively targets M2 macrophages...Mechanistic analysis indicated that its effects are mediated through the activation of the peroxisome proliferator-activated receptor α (PPARα) signaling pathway, leading to suppressed phosphorylation of the NF-κB p65 subunit and c-Jun, which in turn inhibits M2 macrophage polarization. These results uncover a functional mechanism and provide a foundation for developing targeted immunomodulatory therapies against CP."

Journal • Fibrosis • Inflammation • Pancreatitis • JUN • PPARA • S100A9

Open Label Phase 1/2 Study of Tasquinimod in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF) (clinicaltrials.gov) - P1/2 | N=1 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Phase classification: P2 ➔ P1/2

Phase classification • Hematological Disorders • Myelofibrosis • Neutropenia • Thrombocytosis

Active Biotech receives positive feedback on its clinical study with tasquinimod in myelofibrosis (TradingView) - "The study will now resume recruitment...A protocol amendment was submitted to the US Food and Drug Administration (FDA) and the MD Anderson Institutional Review Board. The amendment aims to increase the flexibility in the dosing regimen of tasquinimod and broaden the patient population in the combination cohort of the study. The protocol amendment has now been approved, and the study will resume recruitment. The first patient was recruited in 2025."

Clinical protocol • Enrollment status • Myelofibrosis

Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression. (PubMed, Nat Commun) - "Blocking S100a9 with tasquinimod rescues the defects of Sucnr1 knock-out mice, and combined with a potent Sucnr1 agonist shows therapeutic value in AML mice...Together, Sucnr1 signaling restricts hematopoiesis at least partially through HSPC and via control of S100a8/S100a9. Its dysregulation emerges as contributor to malignancy that opens therapeutic avenues for AML patients."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • S100A8 • S100A9 • SUCNR1

Macrophage-derived S100A9 drives liver fibrosis in Echinococcus multilocularis infection by up-regulating secreted protein acidic and rich in cysteine (SPARC) in hepatic stellate cells. (PubMed, Int J Biol Macromol) - "In vivo, pharmacological inhibition of S100A9 with tasquinimod significantly ameliorated liver fibrosis, down-regulated SPARC expression, and suppressed SMAD2/3 phosphorylation. Critically, histopathological analysis of liver tissues from AE patients confirmed that S100A9 expression was predominantly localized to fibrotic areas and positively correlated with fibrosis severity. Collectively, these results demonstrate that macrophage-derived S100A9 promotes HSCs activation and liver fibrosis via SPARC dependent way, mechanism, and its clinical relevance in human AE substantiates the S100A9-SPARC axis as a potential therapeutic target in AE."

Journal • Fibrosis • Immunology • Infectious Disease • Liver Cirrhosis • Ocular Inflammation • S100A9 • SPARC • TGFB1

Comparative Investigation of Cytotoxic Effects of Structurally Diverse Small Molecules and In Silico Analysis of 1-Acetyl-4-(4-Hydroxyphenyl)piperazine. (PubMed, J Cell Mol Med) - "For comparison, the clinically investigated antimetastatic agent tasquinimod showed moderate activity in 4T1 cells (IC50 = 180.7 μM), serving as a pharmacological benchmark. Notably, despite 4T1's ER-negative status, 1A4HP suppressed cell growth, suggesting possible ER-independent or off-target mechanisms, similar to tamoxifen's secondary effects. Collectively, these results identify 1A4HP as a promising lead compound for further exploration in breast cancers."

Clinical • Journal • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

IgG2a-formatted 4-1BB agonism combined with S100A9 inhibition enhances T cell activation and tumor control in a preclinical model of multiple myeloma (ASH 2025) - P1 | "Tasquinimod(TasQ), a small-molecule immunomodulatory agent, currently evaluated in a phase Ib/IIa clinical trial inMM patients (NCT04405167), offers a complementary strategy...Moreover, co-administration with TasQ enhancedtherapeutic efficacy, supporting the potential benefit of a combinatorial approach. Further investigationis warranted to elucidate the mechanisms driving these responses and to refine 4-1BB-targetedstrategies for effective clinical translation."

IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • CD8 • CD86 • GZMB • S100A9 • TNFRSF9

The transition from myelodysplastic neoplasm to secondary acute myeloid leukemia is revealed by molecular analysis, while functional drug screening demonstrates novel sensitivity patterns with clinical implication (ASH 2025) - "There are only a limited number of agentsthat are FDA approved for treatment of MDS including BCL2 and IDH inhibitors, hypomethylating agents(HMAs), ESAs, luspatercept and imetelstat...For MDS patients, weidentified the most effective agents with the proportion of sensitive samples noted in parentheses:mitoxantrone (100%), olutasidenib (78%), venetoclax (67%), dinaciclib (67%), trametinib (67%), olaparib(56%), GSK3368715 (56%), pacritinib (44%), lenalidomide (44%), fludarabine (55%), tasquinimod (44%),veliparib (44%). For sAML patients, we identified lenalidomide, olutasidenib, GSK3368715 have high DSSsin all tested samples, while fludarabine, fedratinib, tasquinimod, trametinib, veliparib, mitoxantrone andolaparib have high DSSs in 75% of the AML samples...Cancer Research 2024), and our samples included SF3B1 and U2AF1 mutations.Summary This study of the transition of MDS to sAML highlights molecular changes and reveals new drugsensitivity with agents that could be..."

Biomarker • Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • CD34 • FLT3 • JAK2 • NRAS • PTPN11 • SF3B1 • U2AF1

Active Biotech...announced that the US Patent and Trademark Office (USPTO) has issued a notification that the company’s patent application related to a pharmaceutical formulation containing tasquinimod will be granted on 2 December 2025 under the patent number 12,485,095. (Active Biotech Press Release) - "The patent will provide protection and market exclusivity until 2042."

Patent • Multiple Myeloma • Myelofibrosis

HDAC4 drives ferroptosis and fibrosis by inhibiting Foxo3a-GPX4 axis during AKI-CKD progression. (PubMed, Res Sq) - "Here, we investigated the function and mechanism of HDAC4 in ischemia-reperfusion (IR)-induced AKI-CKD progression using Tasquinimod, a highly selective HDAC4 inhibitor, and conditional tubular HDAC4 knockout mice...Inhibition or deletion of HDAC4 restored Foxo3a nuclear localization, upregulated GPX4, and decreased lipid peroxidation. These findings identify HDAC4 as a key mediator linking IR injury to ferroptosis and fibrotic progression, suggesting that targeting the HDAC4-Foxo3a axis may provide a novel therapeutic strategy to prevent the AKI-CKD transition."

Journal • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • Reperfusion Injury • FOXO3 • GPX4 • HDAC4