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

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

Modelling-filtered drug repurposing and first-in-protein SPR validation of histone deacetylase 4 inhibitors for Ataxia-telangiectasia. (PubMed, Biomed Pharmacother) - "Competitive assay with tasquinimod, a known HDAC4 modulator, revealed that asenapine exhibits higher affinity supporting its candidacy for further pharmacological development. These findings underscore the utility of combining repositioning pipelines with real-time affinity quantification to accelerate the discovery of selective HDAC4-targeted therapeutics for Ataxia-Telangiectasia."

Journal • Ataxia • CNS Disorders • Immunology • Movement Disorders • Primary Immunodeficiency • HDAC4

The Peptide-Drug Conjugate M1pep-Tasquinimod Ameliorates Acute Pancreatitis via Selectively Clearing M1-like Macrophages. (PubMed, Biomater Res) - "Furthermore, M1pep-Tasq effectively improves AP by inhibiting M1-like macrophage polarization by suppressing the S100A9-TLR4-MAPK pathway. Overall, we have developed a novel PDC, M1pep-Tasq, with promising applications in clinical settings to treat a range of inflammatory disorders by increasing the efficacy and reducing the toxicity of Tasq."

Journal • Immunology • Inflammation • Pancreatitis • Systemic Inflammatory Response Syndrome • IFNG • S100A9

Open Label Phase 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) - P2 | N=1 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting | N=33 ➔ 1

Enrollment change • Enrollment closed • Hematological Disorders • Myelofibrosis • Thrombocytosis

Preclinical efficacy of tasquinimod-based combinations in advanced myeloproliferative neoplasms (MPN) in blastic phase. (PubMed, Blood Adv) - "The alarmins, S100A8 (A8) and S100A9 (A9), are low molecular weight proteins belonging to the S100 protein family. Notably, cotreatment with TQ and ruxolitinib or OTX015 induced significantly greater survival than treatment with single agents in the NSG mice engrafted with the PDX cells. These findings clearly demonstrate the preclinical efficacy of TQ in advanced MPN-BP cells and create the rationale to further interrogate the efficacy of TQ-based combinations with the current, front-line therapies or novel agents in advanced MPNs with excess blasts."

IO biomarker • Journal • Preclinical • Acute Myelogenous Leukemia • Inflammation • Myeloproliferative Neoplasm • Oncology • CD33 • CD34 • CDKN1A • GFI1 • IL6 • S100A8 • S100A9 • TLR4

Inhibiting the alarmin-driven hematopoiesis-stromal cell crosstalk in primary myelofibrosis ameliorates bone marrow fibrosis. (PubMed, Hemasphere) - "We previously demonstrated that tasquinimod ameliorates the MPN phenotype, reducing splenomegaly and normalizing fibrosis in a JAK2V617F-driven preclinical model...Our data highlight the hematopoietic origin of the inflammatory signals driving fibrosis. These insights pave the way for potential therapeutic strategies targeting inflammatory signaling pathways in MPN to mitigate fibrosis and improve patient outcomes."

Journal • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • S100A8 • S100A9 • TGFB1

S100A9 Inhibition Enhances CAR T-Cell Function and Overcomes Immune Suppression in CLL (SOHO 2025) - "Targeting S100A9 enhances anti-tumor immunity in a murine CLL model by reducing MDSCs, improving T cell function, and generating more effective CAR T cells."

CAR T-Cell Therapy • IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PD-L1 • S100A9

S100A9 promotes resistance to anti-PD-1 immunotherapy in hepatocellular carcinoma by degrading PARP1 and activating the STAT3/PD-L1 pathway. (PubMed, Cell Oncol (Dordr)) - "Our study reveals that S100A9 facilitates immune evasion in HCC by enhancing PARP1 ubiquitination, STAT3 phosphorylation, and PD-L1 expression. Furthermore, combining S100A9 inhibitors with anti-PD-1 antibodies markedly enhances the therapeutic efficacy of ICIs in HCC. These findings highlight S100A9 as a potential therapeutic target for overcoming resistance to immunotherapy in HCC."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • S100A9

Elastin as a Novel Extracellular Matrix From Aberrant HDAC4 Expression in PDGF-BB-Induced Orbital Fibroblasts From Graves' Ophthalmopathy Patients. (PubMed, Invest Ophthalmol Vis Sci) - "GO orbital tissues and GOF treated with either LMK-235 or tasquinimod were examined...Orbital tissues exhibit shared and unique characteristics from other tissues. Our in vitro studies showed that elastin mRNA and protein expression increased in response to PDGF-BB stimulation in GOF which might be due to aberrant HDAC4 levels."

Journal • Ophthalmology • Thyroid Eye Disease • COL1A1 • HDAC4

S100A8/A9 maintains megakaryocytes in an immature state in immune thrombocytopenia (ISTH 2025) - "In an in vitro ITP model, incubation with ITP plasma reduced megakaryocyte maturation and platelet production, effects that were reversed by the S100A8/A9 inhibitor tasquinimod...In both active and passive ITP mouse models, S100A8/A9 inhibition led to faster platelet recovery and more mature megakaryocytes in bone marrow, supporting the therapeutic potential of targeting S100A8/A9 in ITP treatment. Table or Figure Upload"

Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • S100A8 • TLR4