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    2ms
    A Study to Assess an ATX Inhibitor (IOA-289) in Healthy Volunteers (clinicaltrials.gov)
    P1, N=40, Recruiting, iOnctura | Completed --> Recruiting | Trial completion date: Dec 2021 --> Dec 2024 | Trial primary completion date: Sep 2021 --> Dec 2024
    Enrollment open • Trial completion date • Trial primary completion date
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    cambritaxestat (IOA-289)
    9ms
    A Study to Assess an ATX Inhibitor (IOA-289) in Patients With Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P1/2, N=24, Recruiting, iOnctura | Phase classification: P1b --> P1/2 | Trial completion date: Apr 2024 --> Feb 2025 | Trial primary completion date: Oct 2023 --> Dec 2024
    Phase classification • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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    gemcitabine • albumin-bound paclitaxel • cambritaxestat (IOA-289)
    1year
    Autotaxin secretion is a stromal mechanism of adaptive resistance to TGFβ inhibition in pancreatic ductal adenocarcinoma. (PubMed, Cancer Res)
    The autotaxin inhibitor IOA-289 suppressed NF-κB activation in PDAC cells and overcame resistance to galunisertib and gemcitabine. Most importantly, treatment with galunisertib significantly increased plasma levels of autotaxin in patients enrolled in the H9H-MC-JBAJ study, and median progression free survival was significantly longer in patients without an increase of autotaxin upon treatment with galunisertib compared to those with increased autotaxin. These results establish that autotaxin secretion by CAFs is increased by TGFβ inhibition and that circulating autotaxin levels predict response to the combination treatment approach of gemcitabine plus galunisertib.
    Journal • Stroma
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    TGFB1 (Transforming Growth Factor Beta 1)
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    gemcitabine • galunisertib (LY2157299) • cambritaxestat (IOA-289)
    over1year
    Autotaxin inhibitor IOA-289 reduces gastrointestinal cancer progression in preclinical models. (PubMed, J Exp Clin Cancer Res)
    These results indicate that IOA-289 may be an effective drug for the treatment of tumors of the gastrointestinal tract, particularly those characterized by a high degree of fibrosis.
    Preclinical • Journal
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    ANXA5 (Annexin A5)
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    cambritaxestat (IOA-289)
    over1year
    Autotaxin Inhibition with IOA-289 Decreases Breast Tumor Growth in Mice Whereas Knockout of Autotaxin in Adipocytes Does Not. (PubMed, Cancers (Basel))
    This confirms the relevance of results from autotaxin inhibition in the mouse model. We propose that inhibiting autotaxin activity that is derived from cells presenting breast tumors such as fibroblasts, leukocytes, or endothelial cells changes the tumor micro-environment in such a way as to inhibit tumor growth.
    Preclinical • Journal
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    IL6 (Interleukin 6) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • CCL2 (Chemokine (C-C motif) ligand 2) • TGFB1 (Transforming Growth Factor Beta 1) • TGFB2 (Transforming Growth Factor Beta 2)
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    cambritaxestat (IOA-289)
    over1year
    Characterization and translational development of IOA-289, a novel autotaxin inhibitor for the treatment of solid tumors. (PubMed, Immunooncol Technol)
    Our data show that IOA-289 is a novel ATX inhibitor with a unique chemical structure, excellent potency and an attractive safety profile. Our data support the further development of IOA-289 as a novel therapeutic approach for the treatment of cancer, particularly those with a high fibrotic and immunologically cold phenotype.
    Journal
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    cambritaxestat (IOA-289)
    2years
    A Study to Assess an ATX Inhibitor (IOA-289) in Patients With Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P1b, N=24, Recruiting, iOnctura
    New P1 trial • Combination therapy • Metastases
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    CA 19-9 (Cancer antigen 19-9)
    |
    gemcitabine • albumin-bound paclitaxel • cambritaxestat (IOA-289)
    over2years
    Targeting Autotaxin to suppress stromal signaling in the tumor microenvironment to improve outcome to therapy in fibrotic tumor types (AACR 2022)
    The predicted biologically effective dose of IOA-289 has been calculated using PK/PD modelling combining data from preclinical studies and from the phase Ia healthy volunteer study. IOA-289 is scheduled to enter a phase Ib clinical trial in pancreatic cancer.
    CA 19-9 (Cancer antigen 19-9)
    |
    cambritaxestat (IOA-289)