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

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

Identification and Preliminary Characterization of a Novel Tasquinimod Analog that Unexpectedly Induces Mitotic Arrest by Alteration of Microtubule Dynamics. (PubMed, ACS Med Chem Lett) - "FB2 also reduced the rate of microtubule regrowth in cells; however, we are unable to conclude whether this is due to direct binding to tubulin or to some indirect mechanism involving initial interaction with some other target sites. These effects on tubulin dynamics are likely responsible for defects in spindle structure, mitotic arrest, and the observed robust killing of cancer cells."

Journal • Oncology • HDAC4 • S100A9

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

Tasquinimod, an S100A9 Inhibitor, in Combination with Ixazomib, Lenalidomide, and Dexamethasone for Relapsed and Refractory Multiple Myeloma (ASH 2024) - P1 | "We now report preliminary results of tasq in combination with IRd.Methods : In dose escalation, pts were refractory to, intolerant of, or with contraindication to len, pomalidomide (pom), bortezomib, carfilzomib (cfz), and a CD38 monoclonal antibody. The RP2D of tasquinimod in combination with IRd is 1 mg daily after a 1-week run-in period at 0.5 mg daily. Enrollment continues to tasquinimod with IRd, with a goal of enrolling 6 more patients who are refractory to their most recent Imid/PI combination therapy."

Combination therapy • CNS Disorders • Constipation • Dyspepsia • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Malignancies • Infectious Disease • Insomnia • Multiple Myeloma • Nephrology • Oncology • Prostate Cancer • Renal Disease • Respiratory Diseases • Sleep Disorder • Solid Tumor • S100A9

Tasquinimod Improves Erythropoiesis and Mitigates Bone Loss in Myelodysplastic Mice (ASH 2023) - "In conclusion, this study provides the first evidence for an in vivo effect of TASQ in a murine model of MDS, suggesting improved erythropoiesis and positive effects on the bone phenotype. These results warrant further investigations of TASQ in human trials, particularly in MDS patients in whom anemia and bone loss often coexist."

Preclinical • Acute Myelogenous Leukemia • Anemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Osteoporosis • Rheumatology • KIT • NUP98 • S100A9 • TLR4

Dnmt3a-Mutant Haematopoietic Stem and Progenitor Cells Induce Mesenchymal Stromal Cell Senescence through the Production of Alarmins S100A8/A9 (ASH 2023) - "Ongoing studies using the S100A8/A9 inhibitor Tasquinimod are examining the dependency of Dnmt3a-mutant hematopoiesis on alarmin production ex vivo and in vivo. Given that S100A8/A9 are heavily involved in the pathogenesis of acute inflammation and myeloproliferative neoplasms, induction of senescence through the alarmin axis is a mechanistic link between aging, clonal hematopoiesis and haematologic malignancy."

IO biomarker • Stroma • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology • BCL2 • BCL2L1 • CDKN1A • CDKN2A • DNMT3A • IL6 • S100A8 • S100A9 • TNFA

Histone Deacetylase 4 Facilitates AKI-to-CKD Progression via the Induction of Ferroptosis (KIDNEY WEEK 2025) - "Methods Renal tubular deficient mice lacking HDAC4 and tasquinimod, a selective PRMT5 inhibitor, were used to reduce HDAC4 expression or suppress its activation in a unilateral ischemia/reperfusion injury (UIRI) model...Finally, a direct interaction between HDAC4 and Foxo3a was observed. Conclusion HDAC4 facilitates the progression from AKI to CKD vis a mechanism associated with the induction of ferroptosis."

Epigenetic controller • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • Reperfusion Injury • CDH1 • FOXO3 • GPX4 • HDAC4 • KIM1 • SIRT3 • TCF4 • TFRC • VIM

Enhancing CAR-T Therapy in CLL By Modulating the Immunosuppressive Tumor Microenvironment: A Novel Approach with Significant Therapeutic Potential (ASH 2024) - "To evaluate the in vivo immunomodulatory effect of targeting S100-A9, C57BL/6 were injected with splenocytes from Eµ-TCL1 mice and treated with the oral S100-A9 inhibitor, tasquinimod (TasQ)...CONCLUSION : Our study demonstrates that targeting S100-A9 decreases the suppressive TME in CLL. This finding makes S100-A9 inhibitors promising candidates for bridge therapy to improve T-cell fitness and enhance the effectiveness of CAR-T therapy."

Biomarker • IO biomarker • Tumor microenvironment • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • S100A9

Lineage plasticity influences immune evasion through distinct mechanisms in STK11-deficient NSCLC, with myeloid S100A8/A9 pathway driving T-cell dysfunction in poorly differentiated TTF1-low tumors (SITC 2025) - "Patient outcomes for docetaxel and atezolizumab were assessed in OAK and POPLAR clinical trials. After treatment with S100A8/A9 inhibitor tasquinimod, we observed a marked increase in CD4 and CD8 activation (figure 1) and depletion of Tregs and suppressive NK populations.Conclusions Our multiomic analysis demonstrates interactions between STK11 loss and lineage plasticity that significantly influence the immune microenvironment and response to PD1 checkpoint blockade. We highlight S100A8/9 as a key effector of suppressive myeloid cells in the context of STK11 loss, linking its expression to T-cell dysfunction in patient cohorts, scRNAseq analysis, and immunocompetent murine models, in which S100A8/A9 inhibition improves T-cell functionality."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • CTLA4 • ITGAM • KRAS • NKX2-1 • S100A8 • STK11 • TP53

Preclinical data of tasquinimod in combination with T cell activation to be presented at ASH 2025 (Nasdaq) - "Data to be presented demonstrate the enhancement of the anti-tumor effect of T cell activation when combined with tasquinimod. The tumor cells were further decreased, and immune cells such as T and NK cells became more active, leading to an increased therapeutic effect."

Preclinical • Multiple Myeloma

S100A9 enhances tumor immune suppression and cancer cell survival in small cell lung cancer. (PubMed, Cell Death Dis) - "Furthermore, tasquinimod treatment alone or combined with cisplatin significantly enhanced tumor infiltration of activated CD8+ (CD69-positive) T cells. Overall, our results, for the first time, show that S100A9 enhances SCLC progression and metastasis by altering the tumor microenvironment, and its inhibition using tasquinimod alone or in combination with chemotherapy could be developed as a promising therapeutic strategy for SCLC."

Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD69 • CD8 • S100A9

Tasquinimod for the Treatment of Relapsed or Refractory Myeloma (clinicaltrials.gov) - P1 | N=30 | Terminated | Sponsor: University of Pennsylvania | Trial completion date: Jul 2026 ➔ Jul 2025 | Active, not recruiting ➔ Terminated; Slow accrual at the time when sufficient participants were already enrolled to answer the scientific question posed by the study.

Trial completion date • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology